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RADIOLOGÍA www.elsevier.es/rx RADIOLOGÍA ISSN: 0033-8338 Publicación Oficial de la Sociedad Española de Radiología Médica Incluida en Index Medicus/MEDLINE Volumen 51 Núm. 1 Enero-Febrero 2009 SERAM RADIOLOGÍA Radiología. 2009;51(3):e1-e10 Resumen Objetivo: Los signos radiológicos en la hipoxia del neonato a término son característi- cos y difieren de los de los niños mayores. La valoración de los signos de daño hipóxico en las imágenes del cerebro neonatal requiere prestar atención a una serie de signos específicos. Conclusión: Los hallazgos por imagen en los neonatos deben ser valorados de acuerdo a unas normas diferentes de las usadas en los otros grupos de edad. Proponemos cua- tro signos fundamentales como medio para facilitar el diagnóstico de hipoxia en el neonato. © 2008 SERAM. Publicado por Elsevier España, S.L. Todos los derechos reservados. PALABRAS CLAVE Hipoxia; RM; Neonato; Imagen pediátrica *Autor para correspondencia. J.M. Provenzale Department of Radiology, Duke University Medical Center,Box 3808, Durham, NC 27710, USA Publicado en AJR Am J Roentgenol. 2009;192:41-7 ARTÍCULO DE AJR Diagnóstico por imagen de la hipoxia neonatal: una revisión práctica E. Ralph Heinz a y James M. Provenzale a,b a Department of Radiology, Duke University Medical Center, Durham, North Carolina, USA b Departments of Radiology, Oncology, and Biomedical Engineering, Emory University School of Medicine, Atlanta, GA, USA Imaging findings in neonatal hypoxia: a practical review Abstract Objective: The findings of hypoxia in the term neonate are unique; neonatal brain imaging findings differ from those of older children. Evaluation of neonatal brain images for signs of hypoxic injury requires attention to a specific set of signs. Conclusion: Imaging findings in term neonates must be assessed according to different rules from those used in other age groups. Four major signs are proposed as a means of facilitating the diagnosis of hypoxia in the neonate. © 2008 SERAM. Published by Elsevier España, S.L. All rights reserved. KEYWORDS Hypoxia; MRI; Neonates; Pediatric imaging Los signos de hipoxia en el neonato a término son característicos y difieren de los que aparecen en ni- ños más mayores y en la edad adulta. Además, los episodios de hipoxia neonatal frecuentemente pue- den complicarse con fenómenos de hipoperfusión, algo que no es habitual en los niños mayores o en los adultos. Por otro lado, las alteraciones en los neona- tos a término también son distintas de las de los pre- maturos. Por lo tanto, las imágenes de los neonatos a término que han presentado episodios de hipoxia tie-

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Page 1: RADIOLOGÍA OR A OA L D GI Í...Focos de baja señal normal en el brazo posterior de la cápsula interna (flechas) respecto a la de los ganglios basales y tálamos. A B eAJR 51(3)2009.indd

RADIOLOGÍA

www.elsevier.es/rx

RADIOLOGÍA

ISSN: 0033-8338

Publicación Ofi cial de la Sociedad Española de Radiología Médica

Incluida en Index Medicus/MEDLINE

Volumen 51 Núm. 1

Enero-Febrero 2009

www.elsevier.es/rxwww.seram.es

SERAM

SOCIEDAD ESPAÑOLA DE

RADIOLOGÍA

PORTADA generica.indd 1 20/1/09 15:47:24

Radiología. 2009;51(3):e1-e10

ResumenObjetivo: Los signos radiológicos en la hipoxia del neonato a término son característi-cos y difieren de los de los niños mayores. La valoración de los signos de daño hipóxico en las imágenes del cerebro neonatal requiere prestar atención a una serie de signos específicos.Conclusión: Los hallazgos por imagen en los neonatos deben ser valorados de acuerdo a unas normas diferentes de las usadas en los otros grupos de edad. Proponemos cua-tro signos fundamentales como medio para facilitar el diagnóstico de hipoxia en el neonato.

© 2008 SERAM. Publicado por Elsevier España, S.L. Todos los derechos reservados.

PALABRAS CLAVEHipoxia;RM;Neonato;Imagen pediátrica

*Autor para correspondencia. J.M. Provenzale Department of Radiology, Duke University Medical Center,Box 3808, Durham, NC 27710, USA Publicado en AJR Am J Roentgenol. 2009;192:41-7

ARTÍCULO DE AJR

Diagnóstico por imagen de la hipoxia neonatal: una revisión práctica

E. Ralph Heinza y James M. Provenzalea,b

aDepartment of Radiology, Duke University Medical Center, Durham, North Carolina, USA bDepartments of Radiology, Oncology, and Biomedical Engineering, Emory University School of Medicine, Atlanta, GA, USA

Imaging findings in neonatal hypoxia: a practical review

AbstractObjective: The findings of hypoxia in the term neonate are unique; neonatal brain imaging findings differ from those of older children. Evaluation of neonatal brain images for signs of hypoxic injury requires attention to a specific set of signs.Conclusion: Imaging findings in term neonates must be assessed according to different rules from those used in other age groups. Four major signs are proposed as a means of facilitating the diagnosis of hypoxia in the neonate.

© 2008 SERAM. Published by Elsevier España, S.L. All rights reserved.

KEYWORDSHypoxia;MRI;Neonates;Pediatric imaging

Los signos de hipoxia en el neonato a término son característicos y difieren de los que aparecen en ni-ños más mayores y en la edad adulta. Además, los episodios de hipoxia neonatal frecuentemente pue-den complicarse con fenómenos de hipoperfusión,

algo que no es habitual en los niños mayores o en los adultos. Por otro lado, las alteraciones en los neona-tos a término también son distintas de las de los pre-maturos. Por lo tanto, las imágenes de los neonatos a término que han presentado episodios de hipoxia tie-

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2 Ralph Heinz E et al

nen que valorarse desde una perspectiva diferente a las usadas en otros grupos de edad.

En este artículo se proponen 4 signos fundamenta-les interrelacionados, agrupados bajo el término “sig-no 1-2-3-4”, con la intención de facilitar la detección del daño cerebral por hipoxia en el neonato a térmi-no. Los 4 componentes del signo 1-2-3-4 son la hiper-intensidad de los ganglios basales en las imágenes T1, el aumento de señal del tálamo en las imágenes T1, la ausencia o disminución de la intensidad de señal en el brazo posterior de la cápsula interna en las imágenes T1 (signo del brazo posterior ausente), y los signos de restricción del movimiento de las moléculas de agua en las secuencias de difusión.

Antes de seguir adelante, es importante que distin-gamos 2 formas de hipoxia: la hipoxia severa o total y la hipoxia prolongada o parcial. El término “hipoxia severa” hace referencia a una pérdida súbita y total de la oxigenación. Un ejemplo típico es la hipoxia que se produce por el desprendimiento prematuro de pla-centa. El término “hipoxia prolongada” se refiere a una disminución sostenida, aunque incompleta, de la oxigenación. Es la que ocurre durante un parto difícil y prolongado con deceleraciones prolongadas, dece-leraciones tardías repetitivas y disminución del ritmo cardíaco. Aunque las consideremos como fenómenos distintos, ocasionalmente se solapan, y un niño puede mostrar lesiones propias de los 2 tipos de hipoxia.

Características normales en la resonancia magnética del neonato a término

Para reconocer los cambios provocados por la hi-poxia neonatal en la resonancia magnética (RM)

cerebral es necesario que antes nos familiaricemos con el aspecto del cerebro del neonato normal. Después de 37 semanas de gestación, la mitad pos-terior del brazo posterior de la cápsula interna está mielinizado, y es hiperintenso en T1 e hipointenso en T2 (fig. 1). En consecuencia, como mínimo un tercio de la longitud del brazo posterior de la cáp-sula interna ya debe ser hiperintenso en T1 duran-te las primeras 24 h de vida. Pero es importante tener claro que la señal no aumenta antes de las 37 semanas de gestación. Por ello, si no tomásemos en consideración la edad gestacional, no ver la hi-perintensidad del brazo posterior de la cápsula in-terna en niños de 36 semanas, podría inducir a error y sugerir que se está ante un daño por hipoxia (fig. 2).

En el neonato normal, es característico que la se-ñal del tálamo no esté aumentada en las imágenes T1 (fig. 1). A veces puede verse un incremento su-til, pero éste se limita al cuadrante posterolateral del tálamo, donde los núcleos ventrolaterales, si-tuados inmediatamente por dentro de la porción terminal del brazo posterior de la cápsula interna, están mielinizados.

Signos de hipoxia severa total en la resonancia magnética del neonato a término

Aumento de la intensidad de señal de los ganglios basales en las imágenes T1

Se trata del signo fundamental en el neonato que ha presentado una hipoxia severa total, y aparece du-42 AJR:192, January 2009

Heinz and Provenzale

In normal neonates, the thalamus does not typically have increased signal intensity on T1-weighted images (Fig. 1). On occasion, subtly increased signal intensity may be seen, but this increased signal intensity is restricted to the posterolateral quadrant of the thalamus (corresponding to myelination of the ventrolateral nucleus of the thalamus just medial to the terminal portion of the posterior limb of the internal capsule).

MRI Findings in the Neonate with Severe, Total HypoxiaIncreased Signal Intensity of Basal Ganglia on T1-Weighted Images

A cardinal finding in the neonate who has experienced severe, total hypoxia is abnormally increased signal intensity on T1-weighted images of the basal ganglia (Fig. 3) in the first 3 days of life [1]. This finding presumably reflects the fact that the deep gray matter structures (i.e., the basal ganglia and thalamus) are the most metabolically active in the brain. Therefore, these sites are more vulnerable to oxidative stress and show the effects of hypoxia earlier and to a greater degree than the rest of the brain [2]. The increased signal intensity generally persists for 2–4 months after the insult [1]. Although the finding is sensitive for hypoxia, it is nonspecific because it can be seen to a mild degree in normal infants. Furthermore, the finding is also a subjective one; in general, various observers may differ as to the degree to which the signal intensity is abnormal. Stated differently, overlap exists between the MRI findings of some normal infants and some infants with total hypoxia in whom the signal intensity increase is only mild

or moderate. For this reason, the presence of increased basal ganglia signal intensity should be interpreted in the context of the other three diagnostic signs described in the following text.

Increased Signal Intensity in the Thalamus on T1-Weighted Images

The second sign of neonatal hypoxic injury is increased signal intensity in the thalamus on T1-weighted images [3] (Figs. 3 and 4). The thalamus, like the basal ganglia, is another region that is more susceptible to hypoxic injury, making this finding a relatively sensitive and specific sign of hypoxic injury. The abnormal signal intensity is often more subtle than that seen in the basal ganglia in neonates with hypoxia. Sagittal T1-weighted images can be especially helpful in detecting signal abnormalities when volume-averaging artifacts are suspected on axial or coronal images. A

A

Fig. 1—MRI examination in normal 4-day-old full-term boy.A, Axial T1-weighted image shows normally increased signal intensity of posterior limb of internal capsule (arrows) relative to basal ganglia and thalamus.B, Axial T2-weighted image shows foci of normal hypointense signal in posterior limb of internal capsule (arrows) relative to adjacent basal ganglia and thalamus.

B

Fig. 2—Axial T1-weighted image in 2-day-old, 36-week normal premature boy shows hypointense signal in posterior limb of internal capsule (arrow) that is normal for age. Hyperintense signal associated with posterior limb myelination is not expected until week 37 of gestation. Thus, whereas such a finding would be abnormal in a term infant, it is normal in 36-week-old (or younger) infant. This finding is potential pitfall in evaluation of MR scans in infants and emphasizes need to know gestational age of infant when reviewing MR images. This case also illustrates range of variation in signal intensity that can be seen in normal brain; basal ganglia show moderately hyperintense signal, although less than that typically seen in hypoxia. This case is an example of caution that must be exercised in evaluating basal ganglia signal intensity in absence of other signs of hypoxia. It also shows subjectivity and difficulty of evaluating neonatal brain.

Fig. 3— Axial T1-weighted image in 5-day-old full-term girl with severe, total hypoxia. Hyperintense signal is present in both basal ganglia and thalami (arrowheads), indicating deep gray matter hypoxia. Whereas posterior limb of internal capsule on this pulse sequence is normally hyperintense relative to basal ganglia and thalamus, in this infant it is hypointense (black arrows) for two reasons: intrinsic decrease in signal intensity due to hypoxia and abnormally increased signal intensity of basal ganglia and thalamus. Note also areas of increased signal intensity in frontal white matter that represent hypoxic injury. Finally, hyperintense signal intensity consistent with hypoxic injury is also present in occipital cortex (white arrows).

Figura 1 Examen de resonancia magnética en neonato a término de 4 días. A) Imagen axial T1. Aumento normal de la inten-sidad de señal del brazo posterior de la cápsula interna (flechas) respecto a la de los ganglios basales y tálamos. B) Imagen axial T2. Focos de baja señal normal en el brazo posterior de la cápsula interna (flechas) respecto a la de los ganglios basales y tálamos.

A B

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Diagnóstico por imagen de la hipoxia neonatal: una revisión práctica 3

rante los 3 primeros días de vida (fig. 3)1. Probable-mente refleja el hecho que las áreas metabólica-mente más activas del cerebro corresponden a la sustancia gris profunda (ganglios basales y tálamos). Por lo tanto, estas estructuras son más vulnerables al estrés oxidativo y muestran los efectos de la hi-poxia más precozmente y en mayor grado que el resto del cerebro2. El aumento de señal general-mente persiste de 2 a 4 meses después del episodio de hipoxia1. A pesar de su sensibilidad, el signo no es específico de la hipoxia porque puede verse en menor grado en niños normales. Además, también es un hallazgo subjetivo, de modo que el grado de intensidad a partir del cual la intensidad de señal se considere anormal variará de un observador a otro. Dicho de otro modo, en RM las características de los ganglios basales de algunos niños normales son pa-recidas a las de otros que, aunque han presentado una hipoxia total, sólo muestran un aumento de se-ñal leve o moderado. Por este motivo, la interpreta-ción de la intensidad de los ganglios basales debe

hacerse junto con los otros 3 signos diagnósticos que se describen a continuación.

Aumento de la intensidad de señal del tálamo en las imágenes T1

Es el segundo signo de daño por hipoxia en el neo-nato3 (figs. 3 y 4). El tálamo, igual que los ganglios basales, es una región susceptible a la hipoxia, lo que hace que este hallazgo sea un signo relativa-mente sensible y específico de lesión hipóxica. La anormalidad de la señal es a menudo más sutil que en los ganglios basales. Si se sospecha que fenóme-nos de volumen parcial impiden detectar la altera-ción de la señal en los planos axial y coronal, las secuencias T1 en el plano sagital pueden ser espe-cialmente útiles. El rango de aumento de la señal es amplio, desde un grado muy sutil hasta una mar-cada hiperintensidad (fig. 4). Como ya se ha dicho, es importante tener en cuenta que el aumento sutil de la señal en el cuadrante posterolateral del tála-mo en el neonato normal (correspondiente a la mielinización normal del núcleo ventrolateral) debe distinguirse de una hiperintensidad talámica anor-mal, más difusa, en el neonato con hipoxia (fig. 3).

42 AJR:192, January 2009

Heinz and Provenzale

In normal neonates, the thalamus does not typically have increased signal intensity on T1-weighted images (Fig. 1). On occasion, subtly increased signal intensity may be seen, but this increased signal intensity is restricted to the posterolateral quadrant of the thalamus (corresponding to myelination of the ventrolateral nucleus of the thalamus just medial to the terminal portion of the posterior limb of the internal capsule).

MRI Findings in the Neonate with Severe, Total HypoxiaIncreased Signal Intensity of Basal Ganglia on T1-Weighted Images

A cardinal finding in the neonate who has experienced severe, total hypoxia is abnormally increased signal intensity on T1-weighted images of the basal ganglia (Fig. 3) in the first 3 days of life [1]. This finding presumably reflects the fact that the deep gray matter structures (i.e., the basal ganglia and thalamus) are the most metabolically active in the brain. Therefore, these sites are more vulnerable to oxidative stress and show the effects of hypoxia earlier and to a greater degree than the rest of the brain [2]. The increased signal intensity generally persists for 2–4 months after the insult [1]. Although the finding is sensitive for hypoxia, it is nonspecific because it can be seen to a mild degree in normal infants. Furthermore, the finding is also a subjective one; in general, various observers may differ as to the degree to which the signal intensity is abnormal. Stated differently, overlap exists between the MRI findings of some normal infants and some infants with total hypoxia in whom the signal intensity increase is only mild

or moderate. For this reason, the presence of increased basal ganglia signal intensity should be interpreted in the context of the other three diagnostic signs described in the following text.

Increased Signal Intensity in the Thalamus on T1-Weighted Images

The second sign of neonatal hypoxic injury is increased signal intensity in the thalamus on T1-weighted images [3] (Figs. 3 and 4). The thalamus, like the basal ganglia, is another region that is more susceptible to hypoxic injury, making this finding a relatively sensitive and specific sign of hypoxic injury. The abnormal signal intensity is often more subtle than that seen in the basal ganglia in neonates with hypoxia. Sagittal T1-weighted images can be especially helpful in detecting signal abnormalities when volume-averaging artifacts are suspected on axial or coronal images. A

A

Fig. 1—MRI examination in normal 4-day-old full-term boy.A, Axial T1-weighted image shows normally increased signal intensity of posterior limb of internal capsule (arrows) relative to basal ganglia and thalamus.B, Axial T2-weighted image shows foci of normal hypointense signal in posterior limb of internal capsule (arrows) relative to adjacent basal ganglia and thalamus.

B

Fig. 2—Axial T1-weighted image in 2-day-old, 36-week normal premature boy shows hypointense signal in posterior limb of internal capsule (arrow) that is normal for age. Hyperintense signal associated with posterior limb myelination is not expected until week 37 of gestation. Thus, whereas such a finding would be abnormal in a term infant, it is normal in 36-week-old (or younger) infant. This finding is potential pitfall in evaluation of MR scans in infants and emphasizes need to know gestational age of infant when reviewing MR images. This case also illustrates range of variation in signal intensity that can be seen in normal brain; basal ganglia show moderately hyperintense signal, although less than that typically seen in hypoxia. This case is an example of caution that must be exercised in evaluating basal ganglia signal intensity in absence of other signs of hypoxia. It also shows subjectivity and difficulty of evaluating neonatal brain.

Fig. 3— Axial T1-weighted image in 5-day-old full-term girl with severe, total hypoxia. Hyperintense signal is present in both basal ganglia and thalami (arrowheads), indicating deep gray matter hypoxia. Whereas posterior limb of internal capsule on this pulse sequence is normally hyperintense relative to basal ganglia and thalamus, in this infant it is hypointense (black arrows) for two reasons: intrinsic decrease in signal intensity due to hypoxia and abnormally increased signal intensity of basal ganglia and thalamus. Note also areas of increased signal intensity in frontal white matter that represent hypoxic injury. Finally, hyperintense signal intensity consistent with hypoxic injury is also present in occipital cortex (white arrows).

Figura 2 Imagen axial T1 en un niño de 2 días de vida, pre-maturo normal de 36 semanas, que muestra una hipointensi-dad de señal en el brazo posterior de la cápsula interna (fle-cha) normal para su edad. La hiperintensidad asociada con la mielinización del brazo posterior de la cápsula interna no aparece hasta las 37 semanas de gestación. Por tanto, mien-tras que tal hallazgo sería anormal en un niño a término, es normal en niños de 36 semanas (o menores). Este hallazgo es una fuente potencial de error al evaluar las imágenes de re-sonancia magnética en los niños, y recalca la necesidad de conocer la edad gestacional en el momento de interpretar-las. Este caso también ilustra el rango de variación en la in-tensidad de señal que puede verse en el cerebro normal; los ganglios basales muestran una señal moderadamente hiper-intensa, aunque menos que la que se observa característica-mente en la hipoxia. Este caso es un ejemplo de la cautela con la que debe evaluarse la intensidad de señal de los gan-glios basales en ausencia de otros signos de hipoxia. También muestra la subjetividad y dificultad de la valoración del ce-rebro neonatal.

42 AJR:192, January 2009

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In normal neonates, the thalamus does not typically have increased signal intensity on T1-weighted images (Fig. 1). On occasion, subtly increased signal intensity may be seen, but this increased signal intensity is restricted to the posterolateral quadrant of the thalamus (corresponding to myelination of the ventrolateral nucleus of the thalamus just medial to the terminal portion of the posterior limb of the internal capsule).

MRI Findings in the Neonate with Severe, Total HypoxiaIncreased Signal Intensity of Basal Ganglia on T1-Weighted Images

A cardinal finding in the neonate who has experienced severe, total hypoxia is abnormally increased signal intensity on T1-weighted images of the basal ganglia (Fig. 3) in the first 3 days of life [1]. This finding presumably reflects the fact that the deep gray matter structures (i.e., the basal ganglia and thalamus) are the most metabolically active in the brain. Therefore, these sites are more vulnerable to oxidative stress and show the effects of hypoxia earlier and to a greater degree than the rest of the brain [2]. The increased signal intensity generally persists for 2–4 months after the insult [1]. Although the finding is sensitive for hypoxia, it is nonspecific because it can be seen to a mild degree in normal infants. Furthermore, the finding is also a subjective one; in general, various observers may differ as to the degree to which the signal intensity is abnormal. Stated differently, overlap exists between the MRI findings of some normal infants and some infants with total hypoxia in whom the signal intensity increase is only mild

or moderate. For this reason, the presence of increased basal ganglia signal intensity should be interpreted in the context of the other three diagnostic signs described in the following text.

Increased Signal Intensity in the Thalamus on T1-Weighted Images

The second sign of neonatal hypoxic injury is increased signal intensity in the thalamus on T1-weighted images [3] (Figs. 3 and 4). The thalamus, like the basal ganglia, is another region that is more susceptible to hypoxic injury, making this finding a relatively sensitive and specific sign of hypoxic injury. The abnormal signal intensity is often more subtle than that seen in the basal ganglia in neonates with hypoxia. Sagittal T1-weighted images can be especially helpful in detecting signal abnormalities when volume-averaging artifacts are suspected on axial or coronal images. A

A

Fig. 1—MRI examination in normal 4-day-old full-term boy.A, Axial T1-weighted image shows normally increased signal intensity of posterior limb of internal capsule (arrows) relative to basal ganglia and thalamus.B, Axial T2-weighted image shows foci of normal hypointense signal in posterior limb of internal capsule (arrows) relative to adjacent basal ganglia and thalamus.

B

Fig. 2—Axial T1-weighted image in 2-day-old, 36-week normal premature boy shows hypointense signal in posterior limb of internal capsule (arrow) that is normal for age. Hyperintense signal associated with posterior limb myelination is not expected until week 37 of gestation. Thus, whereas such a finding would be abnormal in a term infant, it is normal in 36-week-old (or younger) infant. This finding is potential pitfall in evaluation of MR scans in infants and emphasizes need to know gestational age of infant when reviewing MR images. This case also illustrates range of variation in signal intensity that can be seen in normal brain; basal ganglia show moderately hyperintense signal, although less than that typically seen in hypoxia. This case is an example of caution that must be exercised in evaluating basal ganglia signal intensity in absence of other signs of hypoxia. It also shows subjectivity and difficulty of evaluating neonatal brain.

Fig. 3— Axial T1-weighted image in 5-day-old full-term girl with severe, total hypoxia. Hyperintense signal is present in both basal ganglia and thalami (arrowheads), indicating deep gray matter hypoxia. Whereas posterior limb of internal capsule on this pulse sequence is normally hyperintense relative to basal ganglia and thalamus, in this infant it is hypointense (black arrows) for two reasons: intrinsic decrease in signal intensity due to hypoxia and abnormally increased signal intensity of basal ganglia and thalamus. Note also areas of increased signal intensity in frontal white matter that represent hypoxic injury. Finally, hyperintense signal intensity consistent with hypoxic injury is also present in occipital cortex (white arrows).

Figura 3 Imagen axial T1 en una niña a término de 5 días de vida con hipoxia severa total. La hiperintensidad bilateral de los ganglios basales y los tálamos (cabezas de flecha), in-dica una afectación por hipoxia de la sustancia gris profun-da. Mientras que el brazo posterior de la cápsula interna en esta secuencia de pulso debe ser hiperintensa respecto a los ganglios basales y tálamo, en esta niña es hipointensa (fle-cha negra) por 2 motivos: la disminución intrínseca de inten-sidad de señal debido a la hipoxia y el aumento anormal de intensidad de señal de los ganglios basales y tálamos.Obsérvense también las áreas con intensidad de señal aumentada en la sustancia blanca frontal que representan daño hipóxico. Por último, también se observa una hiperin-tensidad compatible con daño hipóxico en el córtex occipital (flechas blancas).

➔➔

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4 Ralph Heinz E et al

“Signo del brazo posterior ausente”

El tercer signo de hipoxia importante es la ausencia de la hiperintensidad del brazo posterior de la cáp-sula interna en las imágenes T1 en los neonatos de al menos 37 semanas de edad gestacional (fig. 3). La hiperintensidad está asociada con la mieliniza-ción. Este signo fue descrito de forma simultánea e independientemente por Barkovich et al4 y Ruther-ford et al5 y, posteriormente, fue analizado más de-talladamente por Rutherford et al6.

Como se ha discutido anteriormente, el aumento de señal asociado a la mielinización normal en las imágenes T1 es propio de los neonatos de más de 37 semanas de edad gestacional y se observa en la mitad posterior (o como mínimo en un tercio) del brazo posterior de la cápsula interna. Este signo apa-rece normalmente en las primeras 24 h de vida. En las imágenes T2 la señal disminuye, hecho que pue-de ser de utilidad para determinar con más precisión la localización del brazo posterior de la cápsula in-terna. La disminución o la ausencia total de la hiper-intensidad T1, especialmente cuando también falta la hipointensidad normal de las imágenes T2, es una evidencia más del daño hipóxico. Utilizando estos criterios en las imágenes T1 de inversión recupera-ción, Rutherford et al6 concluyeron que “la ausencia de la intensidad de señal normal es un factor de mal pronóstico neurológico con una sensibilidad del 0,90, una especificidad del 1,0, un valor predictivo positi-vo de 1,0 y un valor predictivo negativo de 0,87”.

Aunque en nuestra experiencia el hallazgo es útil para diagnosticar el daño por hipoxia en el neonato,

hay que destacar que hay discrepancias. Así, en un estudio de 10 neonatos con hipoxia, Barkovich et al7 observaron que la intensidad de señal puede ser nor-mal en el brazo posterior de la cápsula interna du-rante las primeras 48 h de vida, lo que resta valor al signo. Es posible que la diferencia entre nuestros ha-llazgos y los de Barkovich et al esté motivada por el momento en el que se realizaron las exploraciones. En nuestro centro, los niños se estudian generalmen-te después de las 48 h del daño hipóxico, a diferen-cia de la serie de Barkovich et al, en la que los estu-dios se llevaron a cabo durante las primeras 48 h. Para añadir más incertidumbre, el signo del brazo posterior ausente no se hizo patente hasta los 4 días de vida en las imágenes T1 de 4 de los 73 neonatos con daño hipóxico de la serie de Rutherford et al6.

En resumen, el signo del brazo posterior ausente es un signo valioso, pero parece ser poco sensible para detectar el daño hipóxico neonatal en los pri-meros días de vida. Un estudio reciente recomienda comparar la señal del brazo posterior de la cápsula interna con la del putamen posterolateral8. En el neonato normal la señal del brazo posterior de la cápsula interna en las imágenes T1 es mayor que la del putamen posterolateral. Los autores observaron que en 15 de los 16 niños con daño hipóxico-isqué-mico esta relación estaba invertida. Por lo tanto, el aumento relativo de la señal en el putamen poste-rolateral respecto al del brazo posterior de la cáp-sula interna (figs. 2 y 5) puede ser un dato sensible para detectar el daño hipóxico-isquémico8.

Cuando la señal del núcleo pálido o del putamen aumenta patológicamente en las imágenes T1, lo ha-bitual es que sea difícil localizar exactamente el brazo posterior de la cápsula interna, que se halla en contacto con los ganglios basales anormales. En tales circunstancias, valorar si es o no normal puede ser complicado, aunque, por lo menos, las imágenes T2 permiten establecer con certeza su ubicación. Las imágenes de inversión recuperación pueden ser una alternativa útil porque permiten ver mejor el brazo posterior que las secuencias T1 habituales6.

Signos de hipoxia en las imágenes de difusión

En la hipoxia severa total la difusión de las molécu-las de agua disminuye en los ganglios basales, en el brazo posterior de la cápsula interna o en el tálamo (fig. 6). Éste es el cuarto de los signos fundamenta-les de la hipoxia neonatal y se manifiesta como áreas de aumento de señal en las imágenes de difusión, y una disminución de los valores del coeficiente de di-fusión aparente9,10. Las imágenes de difusión pueden ser claramente anómalas aun cuando los otros signos descritos no estén presentes o sean sutiles. Los estu-

Figura 4 Imagen T1 en una niña a término de 6 días de vida, con hipoxia severa total y daño fundamentalmente ta-lámico que muestra un aumento de intensidad en ambos tá-lamos.

AJR:192, January 2009 43

Imaging of Neonatal Hypoxia

range of increased intensity can be seen, from the very subtle to the overtly hyperintense (Fig. 4). As mentioned earlier, the normal subtle increase in signal intensity of the posterolateral quadrant of the normal neonate (corresponding to normal myelination of the ventrolateral nucleus of the thalamus) must be distinguished from the more diffuse increase in signal intensity of the abnormal thalamus in the neonate with hypoxia (Fig. 3).

The “Absent Posterior Limb Sign”The third important sign is absence of the

normal increased signal intensity in the posterior limb of the internal capsule on T1-weighted images in a neonate of at least 37 weeks’ gestational age (Fig. 3). This absent posterior limb sign is due to loss of the normal increased signal intensity that is associated with myelination. This finding was independ-ently described by both Barkovich et al. [4] and Rutherford et al. [5] at about the same time and was subsequently elaborated on by Rutherford et al. [6].

As previously noted, the increased signal intensity on T1-weighted images associated with normal myelination is seen in normal neonates after 37 weeks’ gestational age in the posterior 50% (or at a minimum, 33%) of

the posterior limb of the internal capsule. This finding is usually seen within the first 24 hours of life. Corresponding decreased signal intensity may be seen on T2-weighted images, which can be useful in more precisely determining the location of the posterior limb of the internal capsule. Diminished or complete absence of increased signal intensity noted on T1-weighted images, especially in the absence of the normal dark signal intensity on T2-weighted images, can be used as further evidence of hypoxic injury. Using the criteria as applied to inversion recovery T1-weighted images, Rutherford et al. [6] concluded that ”the absence of normal signal intensity predicted abnormal outcome with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87.”

In our experience, this finding has been helpful in the diagnosis of neonatal hypoxia. However, it is worth noting that Barkovich et al. [7] have shown, in a study of 10 hypoxic neonates, that normal posterior limb signal intensity can be seen in the first 48 hours of life. Consequently, those authors place less emphasis on this sign. Perhaps this variance of opinion relates to the difference in timing of imaging in the series by Barkovich et al.

and timing of imaging of most infants in our practice. In the clinical environment in which we practice, infants are generally scanned more than 48 hours after the hypoxic injury, as opposed to within 48 hours as in the series

Fig. 4—Axial T1-weighted image in 6-day old full-term girl with severe, total hypoxia and primarily thalamic injury shows increased signal intensity in both thalami.

A

Fig. 5—4-day-old full-term girl with severe, total hypoxia and persistent seizures. This case also shows some features of partial, prolonged hypoxia pattern.A, Unenhanced axial T1-weighted image shows absence of normal bright signal in posterior limb of internal capsule (long arrows), referred to as “absent posterior limb sign.” In addition, abnormal increased signal intensity is seen in basal ganglia (arrowheads). Both findings are typical of severe, total hypoxia pattern. Relative increase in signal intensity in posterior putamen relative to posterior limb of internal capsule is reported to be one of most sensitive signs of neonatal hypoxia [8]. Curvilinear regions of increased signal intensity in occipital lobes (short arrows) indicate cortical injury, which is typically seen in partial, prolonged hypoxia pattern.B, Axial T2-weighted image shows absence of normal hypointense signal in posterior limb of internal capsule (arrows), corresponding to findings of absent posterior limb sign seen in A. Regions of diminished signal intensity in brain cortex (arrowheads), corresponding to cortical findings indicated in A, are seen to be more obvious and more extensive on this pulse sequence. In addition, note markedly decreased signal intensity in basal ganglia and thalamus, indicative of hypoxic injury.C, Apparent diffusion coefficient (ADC) map shows no restricted diffusion despite marked findings on conventional MRI. ADC values in areas of signal abnormality depicted in B were normal, measuring within 10% of values in white matter that showed normal intensity. Although severe hypoxia is usually associated with restricted diffusion, on occasion (as in this patient) one must rely on other MR pulse sequences to make diagnosis of hypoxia.

CB

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Diagnóstico por imagen de la hipoxia neonatal: una revisión práctica 5

dios seriados con imágenes de difusión en neonatos a término con daño hipóxico han puesto de manifies-to que la restricción de la difusión es un proceso di-

námico, que comienza el primer día de vida y pro-gresa durante la semana siguiente7. Los signos de restricción pueden verse en las primeras 24 h de

AJR:192, January 2009 43

Imaging of Neonatal Hypoxia

range of increased intensity can be seen, from the very subtle to the overtly hyperintense (Fig. 4). As mentioned earlier, the normal subtle increase in signal intensity of the posterolateral quadrant of the normal neonate (corresponding to normal myelination of the ventrolateral nucleus of the thalamus) must be distinguished from the more diffuse increase in signal intensity of the abnormal thalamus in the neonate with hypoxia (Fig. 3).

The “Absent Posterior Limb Sign”The third important sign is absence of the

normal increased signal intensity in the posterior limb of the internal capsule on T1-weighted images in a neonate of at least 37 weeks’ gestational age (Fig. 3). This absent posterior limb sign is due to loss of the normal increased signal intensity that is associated with myelination. This finding was independ-ently described by both Barkovich et al. [4] and Rutherford et al. [5] at about the same time and was subsequently elaborated on by Rutherford et al. [6].

As previously noted, the increased signal intensity on T1-weighted images associated with normal myelination is seen in normal neonates after 37 weeks’ gestational age in the posterior 50% (or at a minimum, 33%) of

the posterior limb of the internal capsule. This finding is usually seen within the first 24 hours of life. Corresponding decreased signal intensity may be seen on T2-weighted images, which can be useful in more precisely determining the location of the posterior limb of the internal capsule. Diminished or complete absence of increased signal intensity noted on T1-weighted images, especially in the absence of the normal dark signal intensity on T2-weighted images, can be used as further evidence of hypoxic injury. Using the criteria as applied to inversion recovery T1-weighted images, Rutherford et al. [6] concluded that ”the absence of normal signal intensity predicted abnormal outcome with a sensitivity of 0.90, a specificity of 1.0, a positive predictive value of 1.0, and a negative predictive value of 0.87.”

In our experience, this finding has been helpful in the diagnosis of neonatal hypoxia. However, it is worth noting that Barkovich et al. [7] have shown, in a study of 10 hypoxic neonates, that normal posterior limb signal intensity can be seen in the first 48 hours of life. Consequently, those authors place less emphasis on this sign. Perhaps this variance of opinion relates to the difference in timing of imaging in the series by Barkovich et al.

and timing of imaging of most infants in our practice. In the clinical environment in which we practice, infants are generally scanned more than 48 hours after the hypoxic injury, as opposed to within 48 hours as in the series

Fig. 4—Axial T1-weighted image in 6-day old full-term girl with severe, total hypoxia and primarily thalamic injury shows increased signal intensity in both thalami.

A

Fig. 5—4-day-old full-term girl with severe, total hypoxia and persistent seizures. This case also shows some features of partial, prolonged hypoxia pattern.A, Unenhanced axial T1-weighted image shows absence of normal bright signal in posterior limb of internal capsule (long arrows), referred to as “absent posterior limb sign.” In addition, abnormal increased signal intensity is seen in basal ganglia (arrowheads). Both findings are typical of severe, total hypoxia pattern. Relative increase in signal intensity in posterior putamen relative to posterior limb of internal capsule is reported to be one of most sensitive signs of neonatal hypoxia [8]. Curvilinear regions of increased signal intensity in occipital lobes (short arrows) indicate cortical injury, which is typically seen in partial, prolonged hypoxia pattern.B, Axial T2-weighted image shows absence of normal hypointense signal in posterior limb of internal capsule (arrows), corresponding to findings of absent posterior limb sign seen in A. Regions of diminished signal intensity in brain cortex (arrowheads), corresponding to cortical findings indicated in A, are seen to be more obvious and more extensive on this pulse sequence. In addition, note markedly decreased signal intensity in basal ganglia and thalamus, indicative of hypoxic injury.C, Apparent diffusion coefficient (ADC) map shows no restricted diffusion despite marked findings on conventional MRI. ADC values in areas of signal abnormality depicted in B were normal, measuring within 10% of values in white matter that showed normal intensity. Although severe hypoxia is usually associated with restricted diffusion, on occasion (as in this patient) one must rely on other MR pulse sequences to make diagnosis of hypoxia.

CBFigura 5 Niña a término de 4 días de vida con hipoxia severa total y crisis convulsivas persistentes. Este caso también mues-tra algunas características del patrón de hipoxia parcial y prolongada. A) Imagen axial T1 sin contraste. No se observa la señal hiperintensa en el brazo posterior de cápsulas internas (flechas largas) o “signo del brazo posterior ausente”. Además, se ob-serva un aumento de señal anómalo en los ganglios basales (cabezas de flecha). Ambos hallazgos son típicos del patrón de hi-poxia total severa. El aumento relativo de la intensidad de señal en la porción posterior del putamen en comparación con el brazo posterior de la cápsula interna se ha descrito como uno de los signos más sensibles de la hipoxia neonatal8. Las regiones curvilíneas con intensidad de señal aumentada en los lóbulos occipitales (flechas cortas) señalan daño cortical, el cual típica-mente se ve en el patrón de hipoxia parcial prolongada. B) Imagen axial T2. No se observa la señal hipointensa normal en el brazo posterior de la cápsula interna (flechas), que se corresponde con el signo del brazo posterior ausente en la figura A. Las regiones con intensidad de señal disminuida en el córtex cerebral (cabezas de flecha) corresponden a los signos corticales de la figura A, aunque en esta secuencia de pulso son más evidentes y extensos. Además, la intensidad de señal disminuye marca-damente en los ganglios basales y los tálamos, signos indicativo del daño hipóxico. C) Mapa de coeficiente de difusión aparen-te (ADC). No hay signos de restricción de la difusión a pesar de los hallazgos en las imágenes de la resonancia magnética con-vencional. Los valores del ADC en las áreas de señal anómala de la figura B fueron normales, con medidas dentro del 10 % de los valores de la sustancia blanca con intensidad de señal normal. Aunque la hipoxia severa normalmente se asocia con difu-sión restringida, de vez en cuando (como en este paciente) se debe confiar en otras secuencias de pulso para hacer el diagnós-tico de lesión por hipoxia.

44 AJR:192, January 2009

Heinz and Provenzale

by Barkovich et al. Notably, Rutherford et al. [6] reported that in four of 73 neonates with hypoxic injury, the absent posterior limb sign was not apparent on T1-weighted images until up to 4 days after birth.

In summary, the absent posterior limb sign is a valuable one, but it appears to be insensitive for the detection for neonatal hypoxia in the first few days of life. More recently, another investigator has advocated comparison of the posterior limb of the internal capsule with the posterolateral puta-

men to assess for hypoxic injury [8]. In the normal neonate, the posterior limb of the internal capsule has increased signal intensity compared with the posterolateral putamen on T1-weighted images. The presence of the opposite relationship—that is, relatively brighter signal in the posterolateral putamen compared with the posterior limb of the internal capsule (Figs. 2 and 5)—has been found to be a sensitive discriminator of

hypoxic–ischemic injury, being seen in 15 of 16 infants with that injury [8].

When abnormally increased signal inten-sity is present in the globus pallidus or putamen on T1-weighted images, it is often difficult to determine the actual site of the posterior limb of the internal capsule, which lies immediately adjacent to the basal gan-glia. In such situations, assessment of whether this structure is normal can be difficult, but the T2-weighted images at least allow its exact location to be reliably determined. Alternatively, inversion recovery images, which appear to improve visuali-zation of the posterior limb of the internal capsule as compared with T1-weighted imaging sequences, can be useful [6].

Findings on Diffusion-Weighted ImagingThe fourth important sign of severe, total

hypoxia is that of restricted diffusion in the basal ganglia, the posterior limb of the internal capsule, or the thalamus (Fig. 6), manifested by bright signal on diffusion-weighted im-ages and reduced apparent diffusion coeffic-ient values on apparent diffusion coefficient maps [9, 10]. Diffusion-weighted imaging sequences can be overtly abnormal when other signs are only subtly abnormal or even normal. Studies using serial diffusion imaging of term neonates with hypoxic injury show the appearance of regions of restricted diffusion is a dynamic process, beginning on day 1 of life and progressing over the next week [7]. Restricted diffusion can be seen in the first 24 hours after birth, but the degree of restricted water diffusion often increases over the first few days of life, frequently achieving maxi-mum decrease in apparent diffusion coeffic-ient values at approximately 5 days. In addition, new regions of restricted diffusion that are not seen on day 1 may evolve in the first week of life.

Nonetheless, diffusion-weighted imaging has limitations. For instance, increased signal intensity on diffusion-weighted images and concomitant decreased apparent diffusion coefficient values are typically seen for only 10–12 days after tissue death [7]. Beyond

A

Fig. 6—Restricted water diffusion consistent with cell death in 29-day old full-term girl with severe, total hypoxia.A, Axial diffusion-weighted image shows hyperintense signal in basal ganglia, thalami, and internal capsule.B, Apparent diffusion coefficient map shows hypointense signal in same structures that are hyperintense in A, confirming that abnormal signal intensity is due to restricted diffusion.

B

AFig. 7—MRI in 8-day-old full-term boy with neonatal hypoxia shows features of both severe, total hypoxia pattern and prolonged, partial hypoxia pattern. This case illustrates that features of both hypoxia patterns can be seen in the same patient.A, Unenhanced axial T1-weighted image shows foci of abnormally increased signal intensity in frontal and parietal regions (arrows), which is typical of partial, prolonged hypoxia pattern. However, in addition, abnormal hyperintense signal is present in both putamina, which is typical of severe, total hypoxia . Abnormal signal intensity is also present in head of caudate nucleus. Signal intensity in posterior limb of internal capsule is normal.B, Axial T2-weighted image shows patchy areas of abnormal signal intensity in frontal and parietooccipital cortex (arrows), corresponding to abnormalities in these regions seen in A. However, putamen and caudate nucleus appear relatively normal, and normal decreased signal intensity in posterior limb of internal capsule is present. In this infant, one is dependent on T1-weighted images to detect abnormal finding in those regions.

B

Figura 6 Restricción de la difusión de agua compatible con muerte celular en una niña a término de 29 días de vida con hipoxia severa total. A) Imagen de difusión axial. Hiperintensidad de los ganglios basales, tálamos y cápsula interna. B) Mapa de coeficiente de difusión aparente. Hipointensidad de las mismas estructuras que son hiperintensas en la figura A, hecho que confirma que la intensidad de señal anómala se debe a restricción de la difusión.

A B C

A B

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6 Ralph Heinz E et al

vida, pero su importancia suele aumentar durante los primeros días, de modo que los valores del coefi-ciente de difusión aparente descienden hasta un mí-nimo aproximadamente a los 5 días. Además, duran-te la primera semana pueden aparecer signos de restricción de la difusión en áreas cerebrales en las que no eran visibles durante el primer día.

Pese a todo, las imágenes de difusión tienen limi-taciones. Por ejemplo, es característico que el aumento de señal en las imágenes de difusión y el descenso concomitante en los valores del coefi-ciente de difusión aparente, sólo sea un hecho du-rante los 10-12 días que siguen a la muerte tisular7. Después, las imágenes de difusión serán normales a pesar de que la lesión persista. En algunos casos, las imágenes comienzan a tener una apariencia normal hacia los 4 días después del daño tisular7. Dicho de otro modo, las imágenes de difusión son útiles cuan-do son anormales, pero el hecho de que no lo sean no excluye la lesión por hipoxia; cuando pese a todo se sospeche el daño por hipoxia, debe darse más valor a los otros 3 signos del complejo 1-2-3-4, que debe escrutarse sistemáticamente en cada neonato a término con una posible historia de hipoxia.

Además de los 4 signos principales que se han des-crito, en casos de hipoxia severa pueden aparecer ocasionalmente otros 2 signos de lesión cerebral. El primero de ellos, mucho menos frecuente que cual-quiera de los patrones de daño focal descritos, es el daño global del cerebro por una intensa afectación, tanto de la sustancia blanca como de la gris. El se-gundo es la lesión de la sustancia gris y blanca para-sagitales, que se caracteriza por una necrosis bila-teral de la corteza y de la sustancia blanca subcortical en la región parasagital, con extensión frecuente hacia las áreas parietooccipitales del ce-rebro11. En función de la gravedad de la afectación, la lesión puede extenderse a las circunvoluciones precebtrales y poscentrales. Este último tipo de le-sión es diferente de otro que también puede tener una localización parasagital, pero que afecta a las regiones frontera (limítrofes) entre los territorios arteriales principales. Este tipo de daño parasagital se describe en este artículo más adelante con mayor detalle, al discutir la hipoperfusión neonatal.

Espectroscopia por resonancia magnética

En los neonatos a término con daño hipóxico-isqué-mico puede aumentar la relación colina/creatina, disminuir el pico de N-acetil-aspartato (NAA) y apa-recer un pico de lactato7. Además, también puede aparecer un pico de glutamina-glutamato. En mayor o menor grado, con la hipoxia cerebral pueden

aumentar las ratios lactato/creatina, lactato/NAA y lactato/colina, y disminuir las ratios NAA/creatina y NAA/colina12. Estas variaciones metabólicas pueden ser patentes en las primeras 48 h de vida y, en el caso del lactato, aumentar progresivamente hasta llegar a un máximo en torno a los 5 días de vida. A partir de entonces, las relaciones entre los meta-bolitos empiezan a normalizarse en la mayoría de los niños afectados, aunque, si bien con un menor grado de afectación, siguen siendo anormales du-rante muchas semanas7. La evidencia sugiere que el aumento de la ratio lactato/creatina en el primer día de vida es un signo de mal pronóstico neurológi-co y es más sensible que la ratio NAA/creatina13. Por lo tanto, la espectroscopia por RM proporciona in-formación valiosa para valorar a los neonatos a tér-mino con sospecha de daño hipóxico-isquémico, es-pecialmente cuando los hallazgos por imagen en la RM convencional son dudosos. No obstante, algunos investigadores han señalado que son necesarios to-davía más estudios en niños normales para determi-nar mejor cuáles son los límites a partir de los cua-les las ratios entre metabolitos son anormales14.

Signos de hipoxia parcial prolongada en la resonancia magnética del neonato a término

En la mayoría de neonatos con asfixia parcial pro-longada, el mecanismo causal es un parto largo y difícil. En ellos la oximetría muestra frecuentemen-te una hipoxemia perinatal. A diferencia de lo que ocurre en los neonatos con hipoxia severa y total, en los que presentan una hipoxia parcial prolonga-da la intensidad de señal de los ganglios basales tiende a ser normal en las imágenes T1 pero a me-nudo muestran cambios corticales más marcados, aunque tengan un daño hipóxico agudo menos pro-fundo (fig. 7). En la tabla 1 se comparan los signos de RM en los ganglios basales y en el córtex de los niños con hipoxia severa total con los de la hipoxia parcial prolongada.

Hay que tener en cuenta que puede verse una combinación de los hallazgos característicos de la hipoxia severa y total (predominantemente anoma-lías en el brazo posterior y ganglios basales) y los de la hipoxia parcial y prolongada (predominantemen-te anomalías corticales) (fig. 7).

Signos de hipoxia en la tomografía computarizada

Aunque su sensibilidad y especificidad son consi-derablemente menores que las de la RM, la tomo-

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Diagnóstico por imagen de la hipoxia neonatal: una revisión práctica 7

grafía computarizada (TC) también puede em-plearse para detectar el daño por hipoxia en el neonato a término. En los neonatos normales, el núcleo pálido, el putamen y la cabeza del núcleo caudado son característicamente hiperdensos res-pecto a la sustancia blanca adyacente; por lo tan-to, lo habitual es que la sustancia gris y la blanca puedan distinguirse fácilmente (fig. 8). Cuando el neonato a término presenta una hipoxia severa, la disminución de la densidad de los ganglios basales es un signo semiológico importante (fig. 9). El dé-ficit energético que lleva consigo la hipoxia pro-voca el fallo de la bomba sodio-potasio depen-diente del ATP. En los ganglios basales, muy sensibles al déficit de energía, el fallo de la bom-ba da lugar a un edema citotóxico (es decir, aumento del agua intracelular y del tamaño de las células)10.

La pérdida de la densidad del córtex es la se-gunda característica típica de la hipoxia severa total. En estos pacientes, el único signo percepti-

Tabla 1 Grados de intensidad de señal anómala en la hipoxia severa total y en la hipoxia parcial prolongada en 2 localizaciones del neonato a término

Localización Hipoxia severa y total Hipoxia prolongada y parcial

Ganglios basales ++++ —Córtex cerebral Normal o ++ + o ++

Los signos + indican grados de intensidad de señal anómala; el signo — indica ausencia de intensidad de señal anómala.

44 AJR:192, January 2009

Heinz and Provenzale

by Barkovich et al. Notably, Rutherford et al. [6] reported that in four of 73 neonates with hypoxic injury, the absent posterior limb sign was not apparent on T1-weighted images until up to 4 days after birth.

In summary, the absent posterior limb sign is a valuable one, but it appears to be insensitive for the detection for neonatal hypoxia in the first few days of life. More recently, another investigator has advocated comparison of the posterior limb of the internal capsule with the posterolateral puta-

men to assess for hypoxic injury [8]. In the normal neonate, the posterior limb of the internal capsule has increased signal intensity compared with the posterolateral putamen on T1-weighted images. The presence of the opposite relationship—that is, relatively brighter signal in the posterolateral putamen compared with the posterior limb of the internal capsule (Figs. 2 and 5)—has been found to be a sensitive discriminator of

hypoxic–ischemic injury, being seen in 15 of 16 infants with that injury [8].

When abnormally increased signal inten-sity is present in the globus pallidus or putamen on T1-weighted images, it is often difficult to determine the actual site of the posterior limb of the internal capsule, which lies immediately adjacent to the basal gan-glia. In such situations, assessment of whether this structure is normal can be difficult, but the T2-weighted images at least allow its exact location to be reliably determined. Alternatively, inversion recovery images, which appear to improve visuali-zation of the posterior limb of the internal capsule as compared with T1-weighted imaging sequences, can be useful [6].

Findings on Diffusion-Weighted ImagingThe fourth important sign of severe, total

hypoxia is that of restricted diffusion in the basal ganglia, the posterior limb of the internal capsule, or the thalamus (Fig. 6), manifested by bright signal on diffusion-weighted im-ages and reduced apparent diffusion coeffic-ient values on apparent diffusion coefficient maps [9, 10]. Diffusion-weighted imaging sequences can be overtly abnormal when other signs are only subtly abnormal or even normal. Studies using serial diffusion imaging of term neonates with hypoxic injury show the appearance of regions of restricted diffusion is a dynamic process, beginning on day 1 of life and progressing over the next week [7]. Restricted diffusion can be seen in the first 24 hours after birth, but the degree of restricted water diffusion often increases over the first few days of life, frequently achieving maxi-mum decrease in apparent diffusion coeffic-ient values at approximately 5 days. In addition, new regions of restricted diffusion that are not seen on day 1 may evolve in the first week of life.

Nonetheless, diffusion-weighted imaging has limitations. For instance, increased signal intensity on diffusion-weighted images and concomitant decreased apparent diffusion coefficient values are typically seen for only 10–12 days after tissue death [7]. Beyond

A

Fig. 6—Restricted water diffusion consistent with cell death in 29-day old full-term girl with severe, total hypoxia.A, Axial diffusion-weighted image shows hyperintense signal in basal ganglia, thalami, and internal capsule.B, Apparent diffusion coefficient map shows hypointense signal in same structures that are hyperintense in A, confirming that abnormal signal intensity is due to restricted diffusion.

B

AFig. 7—MRI in 8-day-old full-term boy with neonatal hypoxia shows features of both severe, total hypoxia pattern and prolonged, partial hypoxia pattern. This case illustrates that features of both hypoxia patterns can be seen in the same patient.A, Unenhanced axial T1-weighted image shows foci of abnormally increased signal intensity in frontal and parietal regions (arrows), which is typical of partial, prolonged hypoxia pattern. However, in addition, abnormal hyperintense signal is present in both putamina, which is typical of severe, total hypoxia . Abnormal signal intensity is also present in head of caudate nucleus. Signal intensity in posterior limb of internal capsule is normal.B, Axial T2-weighted image shows patchy areas of abnormal signal intensity in frontal and parietooccipital cortex (arrows), corresponding to abnormalities in these regions seen in A. However, putamen and caudate nucleus appear relatively normal, and normal decreased signal intensity in posterior limb of internal capsule is present. In this infant, one is dependent on T1-weighted images to detect abnormal finding in those regions.

BFigura 7 Resonancia magnética en un niño a término de 8 días de vida con hipoxia neonatal que muestra características tanto de hipoxia severa total como de hipoxia parcial prolongada. Este caso ilustra cómo los signos característicos de ambos patrones pueden verse en un mismo paciente. A) Imagen axial T1 sin contraste. Se observan focos anómalos de hiperintensi-dad en las regiones frontales y parietales (flechas), lo cual es característico del patrón de hipoxia parcial prolongada. Sin embargo, se añade una hiperintensidad anómala en ambos putámenes, típico de la hipoxia total severa. También la intensi-dad de señal es anómala en la cabeza de los núcleos caudados. La intensidad de señal en el brazo posterior de la cápsula in-terna es normal. B) Imagen axial T2. Áreas parcheadas de señal anormal en el córtex frontal y parietoocipital (flechas), que corresponden a las anomalías vistas en estas regiones en la figura A. Sin embargo, el putamen y el núcleo caudado aparecen relativamente normales, y la intensidad de señal es normal en el brazo posterior de la cápsula interna. En este niño, son las imágenes T1 las que son útiles para detectar los signos de hipoxia.

A

B

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Imaging of Neonatal Hypoxia

that time, diffusion-weighted images appear normal despite the presence of tissue injury. In some instances, diffusion-weighted im-ages again begin to attain a normal appear-ance as early as 4 days after the tissue injury [7]. Stated differently, diffusion-weighted imaging is informative when abnormal find-ings are present. However, normal diffusion-weighted imaging findings do not exclude hypoxia; in such cases, when hypoxia is suspected, reliance on the other three findings of the 1-2-3-4 sign should be increased. These findings should be systematically reviewed in each term neonate with a possible history of hypoxia.

In addition to the four major findings we have described, in severe hypoxic injury two additional findings of cerebral injury may be seen. The first additional finding is that of profound global injury involving both the gray matter and the white matter, a finding that is much less common than any of the focal injury patterns outlined previously. The second additional finding is that of para-sagittal gray and white matter injury, which is characterized by the presence of bilateral cortical and subcortical white matter necrosis in the parasagittal area, often extending into the parietooccipital areas of the brain [11]. These findings, if severe, may extend to the pre- and postcentral gyrus areas. This form of injury is distinct from another type of injury that may also be referred to as parasagittal in location, but which instead involves the border regions between major arterial territories. This type of parasagittal injury is described in more detail in the discussion of neonatal hypoperfusion later in this article.

MR SpectroscopyMR spectroscopy findings in full-term

infants with hypoxic–ischemic injury include elevation of choline relative to creatine, decreased N-acetylaspartate (NAA), and the presence of a lactate peak [7]. These findings can be seen in the first 48 hours of life and, in the case of lactate, peak at about 5 days of life. In addition, a glutamine–glutamate peak can be seen. Ratios that can be altered to various degrees include lactate/creatine, lactate/NAA, and lactate/choline, which are increased, and NAA/creatine and NAA/choline, which are decreased compared with normal infants [12]. Thereafter, metabolite ratios begin to normalize in most infants, although they persist at a diminished degree of abnormality for many weeks [7]. Evidence suggests that an elevated ratio of lactate/

creatine on day 1 of life is a predictor of a poor subsequent neurologic outcome and is more sensitive than an NAA/creatine ratio [13]. Thus, MR spectroscopy provides valuable information in assessing term infants with suspected hypoxic–ischemic injury, especial-ly when conventional MRI findings are equi-vocal. Nonetheless, some investigators have indicated that further studies are needed in normal infants to better determine the upper limits of normal metabolite ratios [14].

MRI Findings in Prolonged, Partial Hypoxia

In most neonates with prolonged, partial hypoxia, the causative mechanism is a pro-tracted and difficult delivery. These patients frequently have decreased perinatal oxygen levels as measured on oximetry. In contrast to neonates with severe, total hypoxia, those with prolonged, partial hypoxia tend to have normal basal ganglia signal intensity on T1-weighted images but often exhibit more marked cortical signal changes, even though they have a less profound acute hypoxic injury (Fig. 7). A comparison of the MRI findings in the basal ganglia and cortex in severe, total hypoxia and prolonged, partial hypoxia is provided in Table 1.

Note that one can see a mixture of the findings characteristic of severe, total hypoxia (i.e., predominantly posterior limb and basal ganglia abnormalities) and those of the prolonged, partial pattern (i.e., predominantly cortical abnormalities) (Fig. 7).

Findings on CTCT can be used to diagnose hypoxia in the

neonate, although it has considerably less sensitivity and specificity than MRI. On CT examination of normal neonates, the globus pallidi, putamina, and heads of the caudate nuclei are typically hyperdense compared with nearby white matter; thus, good gray–white distinction is normally visible (Fig. 8). In severe hypoxia in the term neonate, a decrease in basal ganglia density is an important finding (Fig. 9). Hypoxia results in energy depletion failure of the sodium–potassium–adenosine triphosphatase pump in the energy-sensitive

basal ganglia, with resultant cytotoxic edema (i.e., increased intracellular water and expansion of cells) [10].

Loss of density of cortex is the second hallmark of severe, total hypoxia. Subtle loss of the normally sharp transition from gray matter to white matter at the corticomed-ullary junction may be the only discernible change. Paradoxically, in some instances of laminar necrosis due to hypoxia and cell death, the cortex may have increased linear density. The third major finding is cerebral edema, which usually occurs after marked neonatal hypoxia, severe hypotension, or both [15]. The degree of cerebral edema is typically greater with hypoxia than with hypotension. Cerebral edema can best be detected by the effacement of the sylvian fissures and the perimesencephalic fissures. The swelling is usually seen by 8 hours after the insult and usually reaches a maximum between 72 and 96 hours.

Hypoperfusion States in the NeonateIn neonates, hypoperfusion often accom-

panies hypoxia. Three patterns of hypoper-fusion may be seen in the neonate.

TABLE 1: Degrees of Abnormal Signal Intensity in Severe, Total Hypoxia and Prolonged, Partial Hypoxia in Two Sites of Full-Term Neonatal Brain

Site Severe, Total Hypoxia Prolonged, Partial Hypoxia

Basal ganglia + + + + –

Cerebral cortex Normal or + + + or + +

Note—Plus signs indicate degree of abnormal signal intensity; minus sign indicates no abnormal signal intensity.

Fig. 8—Unenhanced axial CT scan in normal 2-day old full-term boy shows normal appearance of deep gray matter structures (basal ganglia and thalamus) against background of normal low density of deep white matter (arrowheads).

Figura 8 Imagen axial de tomografía computarizada sin contraste en un niño a término normal de 2 días de vida. Las estructuras de sustancia gris profunda (ganglios basales y tá-lamo) tienen una densidad normal que destaca sobre el fon-do de baja densidad normal de la sustancia blanca profunda (cabezas de flecha).

➔➔

➔➔

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8 Ralph Heinz E et al

ble puede ser la pérdida sutil de la transición en-tre la sustancia gris y la blanca, que normalmente es nítida en la unión córtico-subcortical. Paradóji-camente, en algunos casos de necrosis laminar debida a la hipoxia y muerte celular, el córtex pude presentar un aumento lineal de densidad. El tercer hallazgo característico es el edema cere-bral, que normalmente se produce después de una hipoxia neonatal marcada, una hipotensión severa o ambas15. El grado del edema cerebral por hi-poxia es típicamente mayor que el motivado por la hipotensión. El mejor modo de detectarlo es prestar atención a la cisura de Silvio y las cister-nas perimesencefálicas que desaparecen por la inflamación cerebral. La tumefacción se detecta normalmente hacia las 8 h después del episodio de hipoxia y suele alcanzar su máximo entre las 72 y 96 h.

Estados de hipoperfusión en los neonatos

Los episodios de hipoxia en el neonato suelen acom-pañarse de fenómenos de hipoperfusión, que pue-den presentar 3 patrones diferentes.

— El primero de ellos es el de la leucomalacia peri-ventricular, propia de la hipoperfusión de la circulación fetal. Sin embargo, puesto que este artículo está enfocado en los neonatos a térmi-no, y la leucomalacia periventricular normal-mente se produce en edades gestacionales más tempranas (típicamente entre las semanas 28 y 36), no vamos a tratarla.

— El segundo patrón de hipoperfusión se caracteri-za por cambios isquémicos bastante simétricos en los 2 cuadrantes frontales y en cada uno de los 2 cuadrantes posteriores, en las imágenes axiales. Estos cambios se localizan en las zonas frontera entre los territorios de las arterias cere-bral anterior y media, y los de la arteria cerebral media y posterior (fig. 10). Este patrón se ve a menudo en los adultos que presentan hipoperfu-sión, pero también puede verse en niños bajo circunstancias similares.

— El tercer patrón, conocido como “isquemia en territorios frontera profundos”, es característico de los neonatos a término que han experimenta-do daño hipóxico-isquémico. Las lesiones apare-cen típicamente en los centros semiovales y en una localización intermedia entre los ventrículos laterales y el córtex cerebral. Este tipo de daño por hipoperfusión puede ser unilateral o bilate-ral (figs. 10 y 11). En los casos en los que los sig-nos en las imágenes de RM convencional sean sutiles, las imágenes de difusión pueden ser es-pecialmente útiles para hacer el diagnóstico.

46 AJR:192, January 2009

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The first pattern of hypoperfusion is periventricular leukomalacia, which rep-resents hypoperfusion of the fetal circulation. However, because this article focuses on term neonates and periventricular leukomalacia usually occurs earlier in gestation (typically between the weeks 28 and 36), we will not discuss it further here.

The second pattern of hypoperfusion is characterized by fairly symmetric ischemic changes in the two frontal quadrants and symmetric ischemic changes in each of the two posterior quadrants on axial images. These symmetric changes are located at the watershed zones between the anterior–middle cerebral artery territories and the middle–

posterior cerebral artery territories (Fig. 10). This pattern is frequently seen in adults who suffer hypoperfusion but can also be seen in infants under similar circumstances.

The third pattern, termed “deep watershed ischemia,” is more commonly seen in term infants who have suffered hypoxic–ischemic injury. Lesions are typically seen in the centrum semiovale at an intermediate location between the lateral ventricle and the brain cortex. This type of hypoperfusion injury can be unilateral or bilateral (Figs. 10 and 11). In cases in which the findings are subtle on conventional MRI, diffusion-weighted images may be especially helpful in making the diagnosis.

Sonography for Assessment of Hypoxic–Ischemic Injury

Sonography is often used for assessment of the neonate with suspected hypoxic–ischemic encephalopathy because the equipment is portable, it is inexpensive, and it does not sub-ject the infant to a magnetic field or radiation. Findings include increased echogenicity in white matter and resultant increased gray matter–white matter differentiation [16] (Fig. 12). These findings, which can be focal or diffuse, are thought to reflect edema or necro-sis and correspond to abnormalities on MRI. In addition, focal hyperechogenic regions, which can represent infarcts of hemorrhages, can often be identified. In more severely affected neonates, the cortex may become thickened and the distinction between gray matter and white matter less apparent. Abnormalities at this stage typically become more diffuse, are

AFig. 11—Axial proton density–weighted image in 11-day old full-term girl with severe hypoperfusion. A, Unenhanced axial T1-weighted image shows classic string-of-beads sign of deep watershed infarcts accompanied by increased signal intensity (arrows). Increased signal intensity of cortex (arrowheads) represents associated hypoxic damage at that site.B, Axial proton density–weighted image shows corresponding foci of abnormal signal intensity (arrows) in deep white matter regions.C, Coronal apparent diffusion coefficient map shows foci of restricted diffusion (arrowheads) corresponding to deep white matter abnormalities seen in A and B as well as in corpus callosum (arrow).

CB

Fig. 9—Unenhanced axial CT scan in full-term 3-day-old boy with severe, total hypoxia. Note absence of expected increase in deep gray matter structures (i.e., basal ganglia and thalamus) compared with adjacent white matter. Unlike normal infant shown in Figure 8, lateral margin of basal ganglia cannot be distinguished from adjacent white matter. Deep gray matter structures have diminished density, and consequently basal ganglia and white matter have the same CT density.

Fig. 10—Unenhanced axial CT scan in 3-day-old full-term boy with hypoperfusion injury. Low-density regions indicating watershed ischemia (arrows) are seen in parietooccipital regions (long arrows) and in right frontal lobe (short arrow). This pattern is more typically seen in adults than in infants. Unilateral involvement in frontal lobes is variant of more common bilateral pattern.

46 AJR:192, January 2009

Heinz and Provenzale

The first pattern of hypoperfusion is periventricular leukomalacia, which rep-resents hypoperfusion of the fetal circulation. However, because this article focuses on term neonates and periventricular leukomalacia usually occurs earlier in gestation (typically between the weeks 28 and 36), we will not discuss it further here.

The second pattern of hypoperfusion is characterized by fairly symmetric ischemic changes in the two frontal quadrants and symmetric ischemic changes in each of the two posterior quadrants on axial images. These symmetric changes are located at the watershed zones between the anterior–middle cerebral artery territories and the middle–

posterior cerebral artery territories (Fig. 10). This pattern is frequently seen in adults who suffer hypoperfusion but can also be seen in infants under similar circumstances.

The third pattern, termed “deep watershed ischemia,” is more commonly seen in term infants who have suffered hypoxic–ischemic injury. Lesions are typically seen in the centrum semiovale at an intermediate location between the lateral ventricle and the brain cortex. This type of hypoperfusion injury can be unilateral or bilateral (Figs. 10 and 11). In cases in which the findings are subtle on conventional MRI, diffusion-weighted images may be especially helpful in making the diagnosis.

Sonography for Assessment of Hypoxic–Ischemic Injury

Sonography is often used for assessment of the neonate with suspected hypoxic–ischemic encephalopathy because the equipment is portable, it is inexpensive, and it does not sub-ject the infant to a magnetic field or radiation. Findings include increased echogenicity in white matter and resultant increased gray matter–white matter differentiation [16] (Fig. 12). These findings, which can be focal or diffuse, are thought to reflect edema or necro-sis and correspond to abnormalities on MRI. In addition, focal hyperechogenic regions, which can represent infarcts of hemorrhages, can often be identified. In more severely affected neonates, the cortex may become thickened and the distinction between gray matter and white matter less apparent. Abnormalities at this stage typically become more diffuse, are

AFig. 11—Axial proton density–weighted image in 11-day old full-term girl with severe hypoperfusion. A, Unenhanced axial T1-weighted image shows classic string-of-beads sign of deep watershed infarcts accompanied by increased signal intensity (arrows). Increased signal intensity of cortex (arrowheads) represents associated hypoxic damage at that site.B, Axial proton density–weighted image shows corresponding foci of abnormal signal intensity (arrows) in deep white matter regions.C, Coronal apparent diffusion coefficient map shows foci of restricted diffusion (arrowheads) corresponding to deep white matter abnormalities seen in A and B as well as in corpus callosum (arrow).

CB

Fig. 9—Unenhanced axial CT scan in full-term 3-day-old boy with severe, total hypoxia. Note absence of expected increase in deep gray matter structures (i.e., basal ganglia and thalamus) compared with adjacent white matter. Unlike normal infant shown in Figure 8, lateral margin of basal ganglia cannot be distinguished from adjacent white matter. Deep gray matter structures have diminished density, and consequently basal ganglia and white matter have the same CT density.

Fig. 10—Unenhanced axial CT scan in 3-day-old full-term boy with hypoperfusion injury. Low-density regions indicating watershed ischemia (arrows) are seen in parietooccipital regions (long arrows) and in right frontal lobe (short arrow). This pattern is more typically seen in adults than in infants. Unilateral involvement in frontal lobes is variant of more common bilateral pattern.

Figura 9 Imagen axial de tomografía computarizada (TC) sin contraste en un niño recién nacido a término de 3 días de vida con hipoxia severa total. La densidad de las estruc-turas de sustancia gris profunda (ganglios basales y tálamos) no destaca respecto a la sustancia blanca adyacente. A dife-rencia del niño normal que se muestra en la figura 8, los márgenes laterales de los ganglios basales no pueden distin-guirse de la sustancia blanca adyacente. La densidad de las estructuras de sustancia gris profunda está disminuida; por consiguiente, los ganglios basales y la sustancia blanca tie-nen la misma densidad en la TC.

Figura 10 Imagen axial de tomografía computarizada sin contraste de un niño a término de 3 días de vida con daño por hipoperfusión. Áreas de baja densidad por isquemia en territorios frontera (flechas) en las regiones parietooccipita-les (flechas largas) y en el lóbulo frontal derecho (flecha corta). Este patrón es más propio de los adultos que de los niños. La afectación unilateral del lóbulo frontal es una va-riante del patrón más común de afectación bilateral.

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Diagnóstico por imagen de la hipoxia neonatal: una revisión práctica 9

La ecografía en la evaluación del daño hipóxico‑isquémico

La ecografía es una técnica diagnóstica que se utili-za con frecuencia para evaluar al neonato con sos-pecha de encefalopatía hipóxico-isquémica, ya que los equipos son portátiles, es barata y no somete al niño a un campo magnético o a la radiación ionizan-te. Los signos característicos son el aumento de la ecogenicidad de la sustancia blanca y, en conse-cuencia, el aumento del contraste entre la sustan-cia gris y la blanca16 (fig. 12). Estos hallazgos, que pueden ser focales o difusos, pueden estar causa-dos por el edema o la necrosis y se corresponden con las alteraciones visibles en la RM. Además, es frecuente identificar áreas focales de mayor eco-genicidad, que pueden representar infartos o he-morragias. En los neonatos más graves, el córtex puede hacerse más grueso, y el contraste entre la sustancia gris y la blanca menos aparente. Las anomalías en esta fase se hacen típicamente más difusas, son a menudo asimétricas, y se asocian con la pérdida de la nitidez de los surcos y las cisuras principales16.

A pesar de sus ventajas, la ecografía tiene limi-taciones para detectar lesiones y, además, de-pende de la experiencia de quien interpreta las imágenes y de la variabilidad interobservador. En una serie de 47 neonatos, de los que dos tercios lo eran a término o casi a término, se comparó la eficacia de la ecografía con la de la RM y la TC

46 AJR:192, January 2009

Heinz and Provenzale

The first pattern of hypoperfusion is periventricular leukomalacia, which rep-resents hypoperfusion of the fetal circulation. However, because this article focuses on term neonates and periventricular leukomalacia usually occurs earlier in gestation (typically between the weeks 28 and 36), we will not discuss it further here.

The second pattern of hypoperfusion is characterized by fairly symmetric ischemic changes in the two frontal quadrants and symmetric ischemic changes in each of the two posterior quadrants on axial images. These symmetric changes are located at the watershed zones between the anterior–middle cerebral artery territories and the middle–

posterior cerebral artery territories (Fig. 10). This pattern is frequently seen in adults who suffer hypoperfusion but can also be seen in infants under similar circumstances.

The third pattern, termed “deep watershed ischemia,” is more commonly seen in term infants who have suffered hypoxic–ischemic injury. Lesions are typically seen in the centrum semiovale at an intermediate location between the lateral ventricle and the brain cortex. This type of hypoperfusion injury can be unilateral or bilateral (Figs. 10 and 11). In cases in which the findings are subtle on conventional MRI, diffusion-weighted images may be especially helpful in making the diagnosis.

Sonography for Assessment of Hypoxic–Ischemic Injury

Sonography is often used for assessment of the neonate with suspected hypoxic–ischemic encephalopathy because the equipment is portable, it is inexpensive, and it does not sub-ject the infant to a magnetic field or radiation. Findings include increased echogenicity in white matter and resultant increased gray matter–white matter differentiation [16] (Fig. 12). These findings, which can be focal or diffuse, are thought to reflect edema or necro-sis and correspond to abnormalities on MRI. In addition, focal hyperechogenic regions, which can represent infarcts of hemorrhages, can often be identified. In more severely affected neonates, the cortex may become thickened and the distinction between gray matter and white matter less apparent. Abnormalities at this stage typically become more diffuse, are

AFig. 11—Axial proton density–weighted image in 11-day old full-term girl with severe hypoperfusion. A, Unenhanced axial T1-weighted image shows classic string-of-beads sign of deep watershed infarcts accompanied by increased signal intensity (arrows). Increased signal intensity of cortex (arrowheads) represents associated hypoxic damage at that site.B, Axial proton density–weighted image shows corresponding foci of abnormal signal intensity (arrows) in deep white matter regions.C, Coronal apparent diffusion coefficient map shows foci of restricted diffusion (arrowheads) corresponding to deep white matter abnormalities seen in A and B as well as in corpus callosum (arrow).

CB

Fig. 9—Unenhanced axial CT scan in full-term 3-day-old boy with severe, total hypoxia. Note absence of expected increase in deep gray matter structures (i.e., basal ganglia and thalamus) compared with adjacent white matter. Unlike normal infant shown in Figure 8, lateral margin of basal ganglia cannot be distinguished from adjacent white matter. Deep gray matter structures have diminished density, and consequently basal ganglia and white matter have the same CT density.

Fig. 10—Unenhanced axial CT scan in 3-day-old full-term boy with hypoperfusion injury. Low-density regions indicating watershed ischemia (arrows) are seen in parietooccipital regions (long arrows) and in right frontal lobe (short arrow). This pattern is more typically seen in adults than in infants. Unilateral involvement in frontal lobes is variant of more common bilateral pattern.

Figura 11 Imagen axial en densidad protónica en una niña a término de 11 días de vida con hipoperfusión severa. A) Imagen axial ponderada en T1 sin contraste. Imágenes en cuentas de rosario (string of beads sign), características de los infartos en territorios frontera profundos, que se acompañan de un aumento de la intensidad de señal (flechas). La hiperintensidad del córtex (cabezas de flecha) representa el daño hipóxico asociado en esta localización. B) Imagen axial en densidad protónica. Focos de intensidad de señal anormal (flechas) en las regiones de la sustancia blanca profunda que corresponden a los de la imagen anterior. C) Mapa de coeficiente de difusión aparente. Focos de restricción de la difusión (cabezas de flecha) que se corresponden con las anomalías de la sustancia blanca profunda visualizadas en las figuras A y B, además de la restricción del cuerpo calloso (flecha).

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often asymmetric between hemispheres, and are associated with the loss of landmarks such as sulci and major fissures [16].

Despite the advantages of sonography, limitations have been noted with regard to detection of lesions, as well as its dependence on the experience of the individual inter-preting the study and its interobserver varia-bility. In a study of 47 neonates, of whom two thirds were at term or near term, sonography was compared with MRI and CT for the detection of abnormalities and interobserver agreement [17]. CT and MRI had sub-stantially greater sensitivity for the detection of cortical hypoxic–ischemic injury and markedly lower interobserver variability than sonography. Doppler sonography is not routinely used for assessment of neonatal hypoxia at many institutions. However, when used, this technique may identify a decrease in refractive indexes in arteries due to a relative increase in diastolic flow velocities.

A number of other limitations of sonog-raphy for the diagnosis of hypoxic–ischemic injury in the term neonate have been identified. These include that a substantial percentage of sonographic examinations are false-negative studies, its low sensitivity for detecting cortical lesions, and dependence on the skill of the operator performing the test [1].

SummaryThe accurate diagnosis of hypoxic–ische-

mic injury in the term neonate requires knowledge of the normal appearance of the brain at that age on CT and MRI. The patterns differ from both that seen in preterm infants and that seen in the adult brain. This article has highlighted four findings that, in the experience of the authors, are particularly helpful in rendering the diagnosis of hypoxic–ischemic injury in the term neonate.

AcknowledgmentDr. Provenzale would like to acknowledge

his coauthor, E. Ralph Heinz, for his many years of commitment to the field of radiolo-gy. At the age of 80 years, Dr. Heinz’s dedi-cation serves as an inspiration and challenge to investigators of all ages.

References1. Barkovich AJ, Hallam D. Neuroimaging in peri-

natal hypoxic–ischemic injury. MRDD Research Reviews 1997; 3:28–41

2. Johnston MV, Hoon AH. Possible mechanisms in infants for selective basal ganglia damage from asphyxia, kernicterus, or mitochondrial encepha-lopathies. J Child Neurol 2000; 15:588–591

3. Rowland EH, Poskitt K, Rodriguez E, Lipton BA, Hill A. Perinatal hypoxic–ischemic thalamic in-jury: clinical features and neuroimaging. Ann Neurol 1988; 44:161–166

4. Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia: MR findings in the first 10 days. Am J Neuroradiol 1995; 16: 427–438

5. Rutherford MA, Pennock JM, Schwieso JE, et al. Hypoxic ischaemic encephalopathy: early mag-

netic resonance imaging findings and their evolu-tion. Neuropediatrics 1995; 26:183–191

6. Rutherford MA, Pennock JM, Counsell SJ, et al. Abnormal magnetic resonance signal in the inter-nal capsule predicts poor neurodevelopmental outcome in infants with hypoxic–ischemic en-cephalopathy. Pediatrics 1998; 102:323–328

7. Barkovich AJ, Miller SP, Bartha A, et al. MR imag-ing, MR spectroscopy, and diffusion tensor imag-ing of sequential studies in neonates with encepha-lopathy. Am J Neuroradiol 2006; 27:533–547

8. Liauw L, Palm-Meinders IH, van der Grond, et al. Differentiating normal myelination from hypox-ic–ischemic encephalopathy on T1-weighted im-ages: a new approach. Am J Neuroradiol 2007; 28:660–665

9. Robertson RL, Liat B, Barnes PT, et al. MR line-scan diffusion-weighted imaging of term neonates with perinatal brain ischemia. Am J Neuroradiol1999; 20:1658–1670

10. Provenzale JM, Sorenson AG. Diffusion-weighted MR in acute stroke: theoretic considerations and clinical applications. AJR 1999; 173:1459–1467

11. Campistol J, Poo P, Fernández Alvarez E, Carratalá F. Parasagittal cerebral injury: magnetic resonance findings. J Child Neurol 1999; 14:683–685

12. Cheong JLY, Cady EB, Penrice J, Wyatt JS, Cox IJ, Robertson NJ. Proton MR spectroscopy in neo-nates with perinatal cerebral hypoxic–ischemic injury: metabolite peak-area ratios, relaxation times, and absolute concentrations. Am J Neuro-radiol 2006; 27:1546–1554

13. Hanrahan JD, Sargentoni J, Azzopardi D, et al. Cerebral metabolism within 18 hours of birth as-phyxia: a proton magnetic resonance spectrosco-py study. Pediatr Res 1996; 39:584–590

14. Ment LR, Bada HS, Barnes P, et al. Practice pa-rameter: neuroimaging of the neonate. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Prac-tice Committee of the Child Neurology Society. Neurology 2002; 58:1726–1738

15. Lupton BA, Hill A, Roland EH, Whitfield MF, Flodmark O. Brain swelling in the asphyxiated term newborn: pathogenesis and outcome. Pediat-rics 1988; 82:139–146

16. Daneman A, Epelman M, Blaser S, Jarrin JR. Im-aging of the brain in full-term neonates: does sonography still play a role? Pediatr Radiol 2006; 36:636–646

17. Blankenberg FG, Loh NN, Bracci P, et al. Sono-graphy CT, and MR imaging: a prospective com-parison of neonates with suspected intracranial ischemia and hemorrhage. Am J Neuroradiol2000; 21:213–218

A

Fig. 12—Cranial sonography shows typical findings associated with hypoxia in 5-day-old term girl with hypoxic injury.A, Coronal sonogram shows diffuse increase in echogenicity of white matter consistent with edema as well as increased distinction of gray matter (arrows) and white matter.B, Color Doppler sonogram in sagittal orientation shows reversal of diastolic flow, reflecting increased vascular resistance secondary to edema.

B

F O R Y O U R I N F O R M A T I O N

This article is available for CME credit. See www.arrs.org for more information.

Figura 12 Ecografía craneal. Signos típicos de lesión por hipoxia en una niña a término de 5 días de vida. A) Ecografía en el plano coronal. Aumento difuso de la ecogenicidad de la sustancia blanca característica del edema. Aumento del con-traste entre la sustancia gris y la sustancia blanca (flechas). B) Ecografía Doppler color en el plano sagital. Inversión del flujo diastólico que refleja un aumento de la resistencia vascular secundaria al edema.

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Imaging of Neonatal Hypoxia

often asymmetric between hemispheres, and are associated with the loss of landmarks such as sulci and major fissures [16].

Despite the advantages of sonography, limitations have been noted with regard to detection of lesions, as well as its dependence on the experience of the individual inter-preting the study and its interobserver varia-bility. In a study of 47 neonates, of whom two thirds were at term or near term, sonography was compared with MRI and CT for the detection of abnormalities and interobserver agreement [17]. CT and MRI had sub-stantially greater sensitivity for the detection of cortical hypoxic–ischemic injury and markedly lower interobserver variability than sonography. Doppler sonography is not routinely used for assessment of neonatal hypoxia at many institutions. However, when used, this technique may identify a decrease in refractive indexes in arteries due to a relative increase in diastolic flow velocities.

A number of other limitations of sonog-raphy for the diagnosis of hypoxic–ischemic injury in the term neonate have been identified. These include that a substantial percentage of sonographic examinations are false-negative studies, its low sensitivity for detecting cortical lesions, and dependence on the skill of the operator performing the test [1].

SummaryThe accurate diagnosis of hypoxic–ische-

mic injury in the term neonate requires knowledge of the normal appearance of the brain at that age on CT and MRI. The patterns differ from both that seen in preterm infants and that seen in the adult brain. This article has highlighted four findings that, in the experience of the authors, are particularly helpful in rendering the diagnosis of hypoxic–ischemic injury in the term neonate.

AcknowledgmentDr. Provenzale would like to acknowledge

his coauthor, E. Ralph Heinz, for his many years of commitment to the field of radiolo-gy. At the age of 80 years, Dr. Heinz’s dedi-cation serves as an inspiration and challenge to investigators of all ages.

References1. Barkovich AJ, Hallam D. Neuroimaging in peri-

natal hypoxic–ischemic injury. MRDD Research Reviews 1997; 3:28–41

2. Johnston MV, Hoon AH. Possible mechanisms in infants for selective basal ganglia damage from asphyxia, kernicterus, or mitochondrial encepha-lopathies. J Child Neurol 2000; 15:588–591

3. Rowland EH, Poskitt K, Rodriguez E, Lipton BA, Hill A. Perinatal hypoxic–ischemic thalamic in-jury: clinical features and neuroimaging. Ann Neurol 1988; 44:161–166

4. Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia: MR findings in the first 10 days. Am J Neuroradiol 1995; 16: 427–438

5. Rutherford MA, Pennock JM, Schwieso JE, et al. Hypoxic ischaemic encephalopathy: early mag-

netic resonance imaging findings and their evolu-tion. Neuropediatrics 1995; 26:183–191

6. Rutherford MA, Pennock JM, Counsell SJ, et al. Abnormal magnetic resonance signal in the inter-nal capsule predicts poor neurodevelopmental outcome in infants with hypoxic–ischemic en-cephalopathy. Pediatrics 1998; 102:323–328

7. Barkovich AJ, Miller SP, Bartha A, et al. MR imag-ing, MR spectroscopy, and diffusion tensor imag-ing of sequential studies in neonates with encepha-lopathy. Am J Neuroradiol 2006; 27:533–547

8. Liauw L, Palm-Meinders IH, van der Grond, et al. Differentiating normal myelination from hypox-ic–ischemic encephalopathy on T1-weighted im-ages: a new approach. Am J Neuroradiol 2007; 28:660–665

9. Robertson RL, Liat B, Barnes PT, et al. MR line-scan diffusion-weighted imaging of term neonates with perinatal brain ischemia. Am J Neuroradiol1999; 20:1658–1670

10. Provenzale JM, Sorenson AG. Diffusion-weighted MR in acute stroke: theoretic considerations and clinical applications. AJR 1999; 173:1459–1467

11. Campistol J, Poo P, Fernández Alvarez E, Carratalá F. Parasagittal cerebral injury: magnetic resonance findings. J Child Neurol 1999; 14:683–685

12. Cheong JLY, Cady EB, Penrice J, Wyatt JS, Cox IJ, Robertson NJ. Proton MR spectroscopy in neo-nates with perinatal cerebral hypoxic–ischemic injury: metabolite peak-area ratios, relaxation times, and absolute concentrations. Am J Neuro-radiol 2006; 27:1546–1554

13. Hanrahan JD, Sargentoni J, Azzopardi D, et al. Cerebral metabolism within 18 hours of birth as-phyxia: a proton magnetic resonance spectrosco-py study. Pediatr Res 1996; 39:584–590

14. Ment LR, Bada HS, Barnes P, et al. Practice pa-rameter: neuroimaging of the neonate. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Prac-tice Committee of the Child Neurology Society. Neurology 2002; 58:1726–1738

15. Lupton BA, Hill A, Roland EH, Whitfield MF, Flodmark O. Brain swelling in the asphyxiated term newborn: pathogenesis and outcome. Pediat-rics 1988; 82:139–146

16. Daneman A, Epelman M, Blaser S, Jarrin JR. Im-aging of the brain in full-term neonates: does sonography still play a role? Pediatr Radiol 2006; 36:636–646

17. Blankenberg FG, Loh NN, Bracci P, et al. Sono-graphy CT, and MR imaging: a prospective com-parison of neonates with suspected intracranial ischemia and hemorrhage. Am J Neuroradiol2000; 21:213–218

A

Fig. 12—Cranial sonography shows typical findings associated with hypoxia in 5-day-old term girl with hypoxic injury.A, Coronal sonogram shows diffuse increase in echogenicity of white matter consistent with edema as well as increased distinction of gray matter (arrows) and white matter.B, Color Doppler sonogram in sagittal orientation shows reversal of diastolic flow, reflecting increased vascular resistance secondary to edema.

B

F O R Y O U R I N F O R M A T I O N

This article is available for CME credit. See www.arrs.org for more information.

A B C

A

B

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10 Ralph Heinz E et al

para detectar lesiones, y la concordancia inter-observador17. La sensibilidad de la TC y la RM fue sustancialmente mayor para detectar el daño hipóxico-isquémico cortical, y la variabilidad inter observador marcadamente inferior que en la ecografía. En muchas instituciones, la ecografía Doppler no se utiliza de forma sistemática para evaluar la hipoxia neonatal. Sin embargo, si se utiliza, los índices de resistencia arterial pueden estar disminuidos debido a un aumento relativo de las velocidades diastólicas.

Otras limitaciones de la ecografía para detectar las lesiones hipóxico-isquémicas son el importante porcentaje de falsos negativos, su baja sensibilidad para detectar lesiones corticales y la dependencia de la habilidad del operador que realiza la prueba1.

Resumen

Un diagnóstico certero de daño hipóxico-isquémico en el neonato a término requiere conocer el aspecto normal del cerebro a esa edad en la TC y la RM. Los patrones se diferencian de los del niño pretérmino y los del adulto. Este artículo ha destacado 4 signos que, en la experiencia de los autores, son particular-mente útiles para establecer el diagnóstico de daño hipóxico-isquémico en el neonato a término.

Agradecimientos

El Dr. Provenzale quiere agradecer a su coautor, E. Ralph Heinz, sus muchos años de compromiso con la radiología. A la edad de 80 años, la dedica-ción del Dr. Heinz sirve como inspiración y reto para los investigadores de todas las edades.

En la traducción de este artículo han participado escalonadamente: Marta Bonfill, R4 del Servicio de Radiodiagnóstico del Hospital Universitario Dr. Josep Trueta, Girona (traducción del original); Sebastià Re-mollo, Neurorradiólogo del Hospital Universitario Dr. Josep Trueta, Girona (revisión de la traducción); Ana Blanco Barrio, editora adjunta de RADIOLOGÍA (revi-sión de la traducción); Elida Vázquez, editora de imagen pediátrica de RADIOLOGÍA (segunda revisión de la traducción), y José M. García Santos, Editor en Jefe de RADIOLOGÍA (visto bueno a la traducción).

Bibliografía 1. Barkovich AJ, Hallam D. Neuroimaging in perinatal hypoxic–

ischemic injury. MRDD Research Reviews. 1997;3:28-41. 2. Johnston MV, Hoon AH. Possible mechanisms in infants for

selective basal ganglia damage from asphyxia, kernicterus, or mito chondrial encephalopathies. J Child Neurol. 2000; 15:588-91.

3. Rowland EH, Poskitt K, Rodríguez E, Lipton BA, Hill A. Peri-natal hypoxic–ischemic thalamic injury: clinical features and neuroimaging. Ann Neurol. 1988;44:161-6.

4. Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia: MR findings in the first 10 days. Am J Neuro radiol. 1995;16:427-38.

5. Rutherford MA, Pennock JM, Schwieso JE, et al. Hypoxic ischaemic encephalopathy: early magnetic resonance imag ing findings and their evolution. Neuropediatrics. 1995;26:183-91.

6. Rutherford MA, Pennock JM, Counsell SJ, et al. Abnormal magnetic resonance signal in the internal capsule predicts poor neurodevelopmental outcome in infants with hypoxic–ischemic encephalopathy. Pediatrics. 1998;102:323-8.

7. Barkovich AJ, Miller SP, Bartha A, et al. MR imaging, MR spectros-copy, and diffusion tensor imaging of sequential studies in neo-nates with encephalopathy. Am J Neuroradiol. 2006;27:533-47.

8. Liauw L, Palm-Meinders IH, van der Grond, et al. Differen-tiating normal myelination from hypoxic–ischemic ence pha­lo pathy on T1-weighted images: a new approach. Am J Neuro radiol. 2007;28:660-5.

9. Robertson RL, Liat B, Barnes PT, et al. MR linescan diffusion­weighted imaging of term neonates with perinatal brain ischemia. Am J Neuroradiol. 1999;20:1658-70.

10. Provenzale JM, Sorenson AG. Diffusion-weighted MR in acute stroke: theoretic considerations and clinical applications. AJR Am J Roentgenol. 1999;173:1459-67.

11. Campistol J, Poo P, Fernández Álvarez E, Carratalá F. Para­sagittal cerebral injury: magnetic resonance findings. J Child Neurol. 1999;14:683-5.

12. Cheong JLY, Cady EB, Penrice J, Wyatt JS, Cox IJ, Robertson NJ. Proton MR spectroscopy in neonates with perinatal cere-bral hypoxic–ischemic injury: metabolite peak­area ratios, relaxation times, and absolute concentrations. Am J Neuro-radiol. 2006;27:1546-54.

13. Hanrahan JD, Sargentoni J, Azzopardi D, et al. Cerebral meta-bolism within 18 hours of birth asphyxia: a proton magnetic resonance spectroscopy study. Pediatr Res. 1996;39:584-90.

14. Ment LR, Bada HS, Barnes P, et al. Practice parameter: neu-roimaging of the neonate. Report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neu-rology. 2002;58:1726-38.

15. Lupton BA, Hill A, Roland EH, Whitfield MF, Flodmark O. Bra-in swelling in the asphyxiated term newborn: pathogenesis and outcome. Pediatrics. 1988;82:139-46.

16. Daneman A, Epelman M, Blaser S, Jarrin JR. Imaging of the brain in full-term neonates: does sonography still play a role? Pediatr Radiol. 2006;36:636-46.

17. Blankenberg FG, Loh NN, Bracci P, et al. Sonography CT, and MR imaging: a prospective comparison of neonates with sus-pected intracranial ischemia and hemorrhage. Am J Neuro-radiol. 2000;21:213-8.

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