BOLD (blood oxygen level–dependent) in nephrology

7/29/2019 BOLD (blood oxygen leveldependent) in nephrology

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BOLD (blood oxygen leveldependent)

Imaging

Presentor : Venkataramanan

Moderator : Prof. Dr. Sham Sunder


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The renal medulla functions in a hypoxic

milieu and is susceptible to changes in blood

flow and blood oxygenation.

Medullary hypoxia has been implicated as a

common pathway in renal failure in animal

models of various renal diseases, including

hypertension and diabetes.


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BOLD MRI

used for noninvasive but indirect measurement

of renal oxygenation.

exploits the paramagnetic effect of

deoxyhemoglobin for acquisition of images

sensitive to local oxygen concentration.


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With an increase in tissue deoxyhemoglobin

concentration, result in increased magnetic spin,

there is more dephasing and a decrease in the

T2* relaxation time of the protons in thesurrounding tissues

higher tissue oxygenation results in increased T2*

relaxation time and a correspondingly shortervalue (R2*) Magnetic rate of relaxation .


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Magnetic rate of relaxation(R2*) positively

correlates with deoxyhemoglobin levels and

was therefore used as a surrogate measure

of tissue oxygenation.

The increased R2 level implies an increased

deoxyhaemoglobin level and decreased

oxygen bioavailability in the tissue.


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Blue represents the lowest R2 level, indicating the lowest tissue

deoxyhaemoglobin concentration, and green and orange distinctivelyrepresent increasing R2 levels, showing the increase of tissue

deoxyhaemoglobin concentration. In a normal functioning allograft, the

cortex is blue with areas of green and the medulla is green and orange

reflecting the decrease in tissue oxygen bioavailability from outermedulla to inner medulla.


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Furosemide was administered to examine the

effect of inhibiting energy-dependent

electrolyte transport on tissue oxygenation in

subjects.


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RENAL ALLOGRAFT DYSFUNCTION


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The medullary R2* value in patients who have

undergone transplantation is lower than that

in healthy volunteers, implying relatively

improved oxygenation in transplanted

kidneys.

Reduced tubular fractional reabsorption of

sodium and an increase in blood flow due toallograft denervation.


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In early renal dysfunction after transplantation,

differentiating acute rejection from ATN is an

important but difficult clinical endeavor

because the initial manifestations of both of

these conditions are abnormal serum

creatinine concentration and a decrease in

GFR


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Sadowski et al. found that patients with acuterejection have significantly lower R2* values(higher oxygenation) in the medulla than

patients with ATN and normal allografts. Using an R2* cutoff of 18 seconds1 or lower,

the investigators diagnosed acute rejectionwith 100% sensitivity and specificity.

Sadowski EA, Fain SB, Alford SK, et al. Assessment of acute renaltransplant rejection with blood oxygen leveldependent MR imaging:initial experience. Radiology 2005; 236:911919


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This decrease in renal hypoxia in acute

rejection has been attributed to decreased

oxygen utilization or increased

corticomedullary shunting of blood.

In contrast, patients with ATN have higher

cortical R2* value than patients with normal

transplants and patients with acute rejection,likely because of ischemic insult.


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ATN allograft shows increased green areas in the cortex and more

orange areas in the medulla reflecting the decrease in tissue oxygen

bioavailability both in the cortex and in the medulla


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Colour gradient disappears with increased blue areas

in the medulla


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Eighty-two patients with normal graft function

and 28 patients with biopsy-proven AR (n =

21) or ATN (n = 7) were enrolled.

Patients with AR and ATN underwent BOLD

MRI within 6 days before or after kidney

transplant biopsy.

Cortical R2 (CR2) and medullary R2 (MR2)

levels were measured.


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The mean CR2 level was significantly higher in the ATN group

(15.25 1.03/s) compared to the normal group (13.35 2.31/s,

P = 0.028) and AR group (12.02 1.72/s, P = 0.001).


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The mean MR2 level was significantly lowerin the AR group (14.02

2.68/s) compared to the normal group (16.662.82/s, P


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Conclusions

BOLD MRI could be a valuable method to

discriminate between AR and ATN by

measuring tissue oxygen bioavailability in

early kidney allograft dysfunction.


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chronic allograft nephropathy

loss of corticomedullary differentiation on R2*maps of patients with chronic allograftnephropathy with a decrease in medullary R2*

values that approaches cortical R2* values.These changes may reflect a decrease indeoxyhemoglobin in the medulla due todecreased tubular work and underutilization of

oxygen.Djamali A, Sadowski EA, Muehrer RJ, et al. BOLD-MRI assessment of intrarenal

oxygenation and oxidative stress in patients with chronic kidney allograftdysfunction.Am J Physiol Renal Physiol 2007; 292:F513F522


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RENAL ARTERY STENOSIS


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Juillard et al. found a graded increase in

cortical and medullary R2* value in response

to a decrease in renal blood flow in a pig

model.

decrease in cortical and medullary R2* value

with return to baseline values in response to

resolution of renal artery occlusion.


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BOLD MRI -evaluation of RAS in

humans.


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Furosemide was administered to examine the effect ofinhibiting energy-dependent electrolyte transport on

tissue oxygenation in subjects with renovasculardisease.

In 21 kidneys with normal nephrograms, administrationof furosemide led to a 20% decrease in medullary R2*

(P 0.01) and an 11.2% decrease in cortical R2*. In normal-size kidneys downstream of high-grade renal

arterial stenoses, R2* was elevated at baseline, but fellafter furosemide.

This finding suggests maintenance of functionalreserve in kidneys even in the presence of reducedGFR.


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However, atrophic kidneys distal to the totally

occluded renal arteries had a low R2* value

(or improved oxygenation) that did not

respond to furosemide challenge.

Thus, response to furosemide can serve as a

marker of maintained renal function in the

presence of RAS.


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Given the recent concerns with nephrogenicsystemic fibrosis (NSF) - use of contrastenhanced MRA and evaluation of GFR in

subjects with compromised renal functionneed additional caution.

Non-contrast methods, such as BOLD MRI,may provide important alternative techniques

for investigating vascular compromise andrenal functional status.


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Diabetic nephropathy


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Using BOLD MRI, Ries et al. found significantly

lower oxygenation in the renal medulla of

diabetic rats than in a control group as early as

5 days after induction.

Epstein et al. found a significant increase in

oxygenation of the renal medulla in healthy

subjects in response to water diuresis. Thisresponse was absent in the diabetic patients.


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Epstein et al studied of eighteen human subjects(nine healthy non-diabetics and nine with mild,controlled diabetes)

In healthy subjects , water-diuresis led to a

significant increase in the oxygenation of therenal medulla, but not in the diabetic patients asevaluated by BOLD MRI.

These results suggest that even patients with

mild diabetes already show signs of renal injurylong before the onset of symptoms that usuallyaccompany kidney disease.


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Studies are being conducted to explore the

role of nitric oxide synthase and nitric oxide

inhibitors in animal models and diabetic

patients to better understand the role of nitricoxide in the pathogenesis of diabetes.


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Hypertension

Animal studies have shown that medullary

blood flow is decreased in hypertension and,

more importantly, that reduced medullary

blood flow is sufficient to produce

hypertension.


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Tempol (4-hydroxy-2,2,6,6-tetramethyl

peridinoyl) is a superoxide scavenger and is

known to improve NO bioavailability. Short- and long-term administration of tempol

has been shown to increase medullary blood

flow in hypertension rats by 35

50% andreduce mean arterial pressure (MAP) by 20

mmHg .


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Tempol showed no effect on the R2* in

normal rats but significantly decreased in

hypertensive rats evaluated by BOLD MRI.


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Moreover, the complexity of the relationshipbetween renal oxygenation, severity of CKD, and

etiology of the underlying renal disease may require

that subjects be categorized not only by stage of CKD

but also by its underlying etiology.


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Limitations

BOLD signal intensity is an indirect marker of

renal oxygenation, and various factors

influence signal intensity on BOLD images.

These factors include oxygen supply and

consumption, blood flow, hematocrit, and

plasma oxygen (Po2).

Therefore, direct calibration of R2* valueversus Po2 is unreliable.


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The absolute magnitude of the R2* value is

less reliable in practice than the relative

changes observed in response to various

physiologic and pharmacologic challenges.

More work needs to be done to better

understand whether changes in BOLD signal

intensity in renal disease result from changesin oxygen supply or oxygen consumption


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Summary

BOLD MRI is an endogenous contrast

mechanism and allows for rapid, noninvasive

means to assess intra-renal oxygenation in

humans.

Important applications in understanding renal

physiology and patho - physiology, and in turn

lead to the development of novelinterventional strategies.


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Identifying kidneys that maybe amenable to

functional recovery by restoring blood flow in

cases with renal artery stenosis

Distinguishing between acute rejection from

acute tubular necrosis in renal transplants.

Bold MRI imaging promises to become an

important tool for monitoring renaloxygenation in various clinical scenarios.


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Documents

BOLD (blood oxygen level–dependent) in nephrology