“Dr. Beckman has single-handedlychanged the course of science andtechnology in this country,” notes Dr.Berns. “His record of inventions andhis record of philanthropy are bothunsurpassed. Everything we do here[at BLI] bears his imprint in someway, and I feel lucky to have Dr.Beckman as a friend and mentor.”

(newsbriefs continued on p. 7)

I N T H E N E W S

Director’s Message 2

Breast Cancer Detection 3

ODT: Glimpsing the Skin 4

Fall 2000

NelsonElected toASLMS

Presidency

1

Newsbriefs A CENTURY OF EXCELLENCE

Faculty and staff gathered at theBeckman Laser Institute on April

18, 2000, to celebrate the 100th birth-day of BLI co-founder Dr. Arnold O.Beckman. Cake and champagne wereserved in honor of Dr. Beckman’s“century of excellence,” and InstituteDirector Michael Berns, Ph.D., was onhand to make the toast.

B E C K M A N L A S E R I N S T I T U T E

M embers of the AmericanSociety for Laser Medicine

and Surgery (ASLMS) have elected J.Stuart Nelson, M.D., Ph.D., to serveas the next president of their organi-zation. Dr. Nelson will serve as Presi-dent-Elect for the remainder of 2000and will assume the President’smantle when the organization con-venes for its annual meeting in NewOrleans next spring.

With more than 4,000 members,ASLMS is the world’s largest profes-sional organization for research, edu-cation, and clinical care in the fieldof laser medicine. The society crossesdisciplinary borders, drawing itsmembers from a variety of medicaland surgical fields as well as nursing,dentistry, veterinary medicine, indus-try, research, and government.

As President, Dr. Nelson will pre-side at all meetings of the ASLMSmembership. “I’m honored to serveASLMS and its members in this ca-pacity,” says Nelson, who will also becalled upon to organize the annualmeeting of the ASLMS in spring 2002.

Institute Director Michael Berns,Ph.D., a past President of ASLMShimself, understands the rigors andthe responsibilities of the office. “Dr.Nelson will be busy, but I’m sure heis the right person for the job. It’sgratifying to see a former student re-ceive accolades for his work, and Ithink his election confirms the excel-lent reputation which BLI enjoys withprofessionals in the field.” ■

Institute co-founder Arnold O. Beckman, Ph.D. (seated, center)celebrates his 100th birthday with staff and faculty at the BeckmanLaser Institute, April 18, 2000 (see newsbrief below).

2

D I R E C T O R’ S M E S S A G E

Beckman Laser Institute and Medical ClinicUniversity of California, Irvine

1002 Health Sciences Road East, Irvine, CA 92612(949) 824-4713 (Administration) (949) 824-7980 (Clinic)

http://www.bli.uci.edu

Board of DirectorsLinda Cahill, Chairman

Arnold O. Beckman, Ph.D., Chairman EmeritusMichael W. Berns, Ph.D., President, CEO, and Vice Chair

George E. Hewitt, Secretary/Treasurer

George L. Argyros Brian R. Demsey Richard A. Nesbit, Ph.D.Patricia Beckman Harry Gray, Ph.D. Robert L. Stoy, Ph.D.

Thomas C. Cesario, M.D. Gavin S. Herbert David S. Tappan, Jr. Richard P. Kratz, M.D.

AdministrationMichael W. Berns, Ph.D., President and CEO

J. Stuart Nelson, M.D., Ph.D., Associate DirectorRuth Bundy, Ph.D., R.N., Clinic Administrative Director

George M. Peavy, D.V.M., Veterinary DirectorRachel Schreiman, C.P.A., M.B.A., Director of Finance

Joyce Zeiler, R.N., Nurse Director

Beckman Laser Institute NewsAlexander Karn

A Voice From the Past Says, ‘Time for a Change!’by Michael Berns, Ph.D.Arnold and Mabel Beckman ProfessorPresident and Director

Moving to a new home affordsus the opportunity to come

across valuable things we forgot wehad. While packing boxes with mywife, Robbie, to prepare for our re-cent move, I came across an audio-tape that my close friend Doug Nash(thanks, Doug!) made at the BLIopening ceremonies fifteen years ago.

The tape still sounds great, and soI am enclosing along with this news-letter a transcription of the com-ments made by Institute co-founder,Dr. Arnold O. Beckman (now 100

years young). I think you will find Dr.Beckman’s comments both enjoyableand illuminating.

With his characteristic wit, Dr.Beckman explains why he es-

tablished BLI as a separate, non-profitcorporation with a unique businessrelationship to the University of Cali-fornia. The nervous laughter of uni-versity officials and friends of UCIcan be heard in the background.

Dr. Beckman points out that BLIwas conceived as an experiment and,as such, was born with the capacityto either succeed or fail. Fifteen yearslater, I think it’s time we evaluate theresults.

The success of the Institute is re-flected in the numerous researchachievements made here, as well asthe publications, awards, and honorswhich our faculty and students havewritten and earned over the years.

With respect to technology trans-fer, we can be proud of our patentrecord and of the numerous technolo-gies that have moved from our labsto the real world of patients and busi-ness. And with regard to our clinicalrecord, what figure better illustratesour success than the 20,000 patientswho have been treated at BLIMC forvarious ailments and conditions withour state-of-the-art laser technology?

If any, the failure of the Institutehas been its unwillingness to capitu-late in the face of an ever-changinghealth care environment where bothpatients and physicians are held cap-tive by providers and business strat-egies that are inconsistent with thehigh standards of academic research,patient care, and instruction.

So then, fifteen years into our “ex-periment,” the time seems right for acourse adjustment. We are returningto the most basic precept of the BLImission: that is, basic and clinical re-search “under a single roof.” Havingadded the new Photonics Incubator,we at BLI now have the capability to:(1) pursue the basic research thatleads to new diagnostic and treat-ment modalities; (2) test these newtechnologies and concepts on patientsin our “research clinic” and; (3) de-velop the potential of these technolo-gies with our corporate partners inthe Photonics Incubator. ■

Lasers to Enhance Breast Cancer Detection

C L I N I C A L U P D A T E

3

According to the National CancerInstitute, one in eight women in

the U.S. will be diagnosed with breastcancer. Despite education programsand improvements in diagnostic tech-nologies, breast cancer remains themost common form of cancer amongwomen. In fact, the incidence of thedisease has been rising over the pasttwo decades. As a result, the “fightfor a cure” has become a top priorityat cancer research facilities across thenation and around the world.

Scientists at the University of Cali-fornia, Irvine have taken a leadershiprole in this effort. Led by Bruce J.Tromberg, Ph.D., Director of the La-ser Microbeam and Medical Program(LAMMP) at the Beckman Laser In-stitute, and John A. Butler, M.D.,UCI’s Chief of Surgical Oncology, agroup of UCI researchers is workingto develop a new technique that useslaser light to find and characterize tu-mors in breast tissue.

The Stories Lasers TellPhoton Migration Spectroscopy

(PMS) uses near-infrared light to as-sess physiology and structure indense tissues such as the humanbreast. As light waves propagatethrough these tissues, bundles oflight known as photons are absorbedand scattered by the biological mate-rials they encounter. PMS “trans-lates” absorption and scattering datato provide functional images of vi-tal physiological parameters.

“It sounds difficult, but the basicidea is easy to understand,” Trombergexplains. “We shine a near-infrared

laser on the skin surface;light waves penetrate andmove painlessly throughthe tissue; and when thesewaves exit, they have astory to tell about whatthey encountered on theirjourney.”

In the field of cancer re-search, this “story” couldprovide clinicians with in-formation they can onlycollect at present with acombination of mammog-raphy and surgical biopsy.

“First of all, mammog-raphy does not work aswell in younger womensince they tend to havedenser breast tissue thanpostmenopausal women,” Butlersays. “This leads to greater uncer-tainty in determining whether tu-mors are cancerous or benign.”

Since PMS provides unique func-tional information, the techniquecould be used in conjunction withother methods to improve diagnos-tic accuracy. For example, PMS scanscould be performed at the patient’sbedside to help minimize the largenumber of surgical biopsies per-formed in the United States.

Improving Risk AssessmentTromberg and his research team

are currently conducting clinicalstudies in an effort to assemble an“optical properties” database whichthey will use later to correlate rawdata collected via PMS to meaning-ful diagnostic criteria.

“We have to train ourselves to rec-ognize significant data patterns asnew samples are collected. We are lit-erally writing the book on the opticalproperties of breast tissue as we worktoward assembling reliable diagnos-tic criteria,” Tromberg explains.

Tromberg hopes that PMS caneventually improve risk assessmentfor women with a history of breastcancer in the family. Because it moni-tors biological processes taking placewithin the breast, PMS could signifi-cantly improve current understand-ing of physiological changes associatedwith disease development and theimpact of new therapies.

“Because light is so sensitive to tis-sue function, we are literally taking anew ‘look’ into all aspects of breastdisease: prevention, diagnosis, andtreatment,” Tromberg says. ■

A portable laser scanner is used to locate andcharacterize tumors and other abnormalities in breasttissue.

4

R E S E A R C H U P D A T E

Glimpsing the Skin: ODT and Microvascular Monitoring

Every medical imaging techniquehas its drawbacks, and each fills

a particular niche. For example, ra-dio-frequency and ultrasound imag-ing provide safe, low-cost visualizationof basic anatomy, but resolution forthese techniques is relatively poor. Bycontrast, short wavelength tech-niques, such as x-ray and ionizingradiation, yield greatly improvedresolution, but these can damage liv-ing tissues and degrade biologicalsamples.

Optical imaging technology, theuse of light packets (photons) to “see”inside the human body, offers re-searchers and clinicians a middleroad: high-resolution capabilitieswithout the risks associated withshorter wavelength techniques.

Until recently, however, opticalimaging techniques, e.g., optical co-herence tomography (OCT), were notsuitable for functional imaging of tis-sue anatomy and physiology. Scien-tists could use light-reflectivity togenerate structural images, but noinformation about physiologicalevents and processes inside these tis-sues was available. Researchers at theBeckman Laser Institute have madeit their mission to change this.

Without Making an IncisionOptical Doppler Tomography (ODT)is a new imaging modality whichcombines the principles of OCT withDoppler velocimetry to image tissuestructure and measure blood flowand microcirculation at the same time.Zhongping Chen, Ph.D., AssistantProfessor of Surgery at BLI, heads a

team of researchers working to makeODT a viable tool for the diagnosisand management of disease.

“Science moves ahead when webring new questions to existingknowledge,” Chen explains. ODT canquickly collect high-resolution im-ages of tissue micro-structures (e.g.,the orientation and size of tiny arter-ies and veins) as well as data forblood flow velocity (hemodynamics).

The technique i tsel f is quitesimple. Harmless light is deliveredinto the skin via a hand-held appli-cator. A second beam of light is emit-ted by the applicator to survey theprogress of the first. The interactionof these two beams provides raw in-formation about tissue structure andphysiology. Complex algorithms arethen used to transform this data intoworking, real-time images.

“To the best of our knowledge, this

is a first,” says Chen. “Never beforehas it been possible to provide bloodflow images and velocity profiles ona real-time scale in vivo. We can nowmonitor tissue microvasculaturewithout making an incision, withoutexposing patients to dangerous radia-tion, really, without any specialpreparation at all.”

Getting Under Our SkinAlthough ODT has not yet beentested in a clinical setting, the tech-nique promises to have broad appli-cations for medical diagnostics andphysiological monitoring. Because itoffers resolution levels at or near thelevel of standard histopathology,ODT might be able to eliminate theneed for certain surgical biopsies.

As with OCT, ODT can be used toidentify normal versus neoplastic

(continued on p. 7)

Zhongping Chen, Ph.D., poses in front of his Optical Doppler Tomography (ODT)instrumentation. This technology can be used to image tissue structure and measureblood flow simultaneously.

5

S T A F F P R O F I L E

Institute Contributors and PartnersGOV’T AGENCIES AND FOUNDATIONSArnold and Mabel Beckman Fndn.

The David and Lucile Packard Fndn.Department of Commerce

Department of Defense (ONR)Department of Energy

The George E. Hewitt Fndn. forMedical Research

Hester Family FoundationHoag Foundation

National Institutes of HealthWhitaker Foundation

SUPPORTERSDr. and Mrs. Jay Applebaum

The Argyros FoundationDr. Arnold O. Beckman

Patricia BeckmanDr. and Mrs. Michael W. BernsDr. and Mrs. Matthew Brenner

Mr. and Mrs. Nathaniel BrennerMarilyn Burton

Cheng-Jen Chang, M.D.The John Chao Family

Dr. and Mrs. W. Andrew CiesDr. Howard and Rita ConnMr. and Mrs. Duke Cooper

Mr. and Mrs. Brian DemseyDr. and Mrs. Norman Frankel

Mrs. Frederick GarryMr. and Mrs. Walter Gerken

Marilyn Hester GianuliasDr. and Mrs. Frederick Grazer

Mr. and Mrs. Gavin HerbertNora Hester

Mr. George HewittRobert L. Jones, M.D.

Dr. and Mrs. Richard KasperMr. and Mrs. Robert KleistDr. and Mrs. Richard KratzWallace Landholm, M.D.

Richard McCleary and Ileen FrankelFrank and Linda Meyskens

Mrs. Warren S. Myers & FamilyTricia and Al Nichols

Richard and Hinda Rosenthal FoundationMrs. Audrey M. Schneiderman

Mr. and Mrs. Robert W. SchollerMr. and Mrs. John Stahr

Mr. and Mrs. Robert StermanThomas T. and Elizabeth C. Tierney

D.E.L.T.A. RescueOrange Coast Rhodesian Ridgeback Club

Premier Laser Systems, Inc.

Shoreline Dog Fanciers AssociationS. California Veterinary Medical Assoc.,

Orange County ChapterS. California Veterinary Medical Assoc.,Saddleback-Capistrano Valley Chapter

INCUBATOR CORPORATE PARTNERSCandela CorporationNewport CorporationPhotoSense L.L.C.

CORPORATE AFFILIATESAllergan, Inc.

Beckman Coulter, Inc.Coherent, Inc.

ESC Sharplan Lasers, Inc.SmithKline Beecham

INDUSTRIAL ASSOCIATESBio-Safe America

CandelaCarl Zeiss, Inc.

DUSA Pharmaceuticals, Inc.Hewlett Packard

Medical Optics, Inc.Olympus

Physical Optics Corporation

Richard Diaz: Making Chaos Compute

Shall we call it Diaz’s Law? Afixed principle in the BLI uni-

verse? A rule with no exceptions? Atprecisely the moment he sits down athis desk or stops to pop an Altoid intohis mouth--just when he wonders atthe silence--there comes a distress callacross the BLI intercom: “RichardDiaz, please dial 9-0.”

These S.O.S. signals are a regularfeature of Richard’s work day. AsBLI’s computer resource specialist,Richard puts out digital fires largeand small. Lost files, fried disks,crashed systems, and cranky printers:these are Richard’s strong suit.

“Computers have always beenpart of my life,” he says, “although I

only decided to start a career in thefield recently.” Since then, the long-time Orange County resident hasn’thad much time to spare. “I love in-teracting with people,” Richard ex-plains. “And I don’t mind being indemand because the environment atBLI is great. We’re very lucky here.”

“Single and loving it,” Richardcurrently lives in Fullerton with hissix year-old cocker spaniel, Lucky, al-though the two are planning a moveto Long Beach.

An avid baseball fan, Richard es-timates that he will have seen fifty-five Angels’ games by the time thepennant race wraps up in September.“I’m a life-long Angel,” Richard says

proudly. “Whether it’s work or play-ing beach volleyball or organizing agroup excursion to Edison Field, I liketo stay busy.” ■

Richard Diaz, Computer ResourceSpecialist.

6

P H O T O N I C I N C U B A T O R

New Patent for LMS Spawns Marketing Possibilities

BLIMC Faculty Chairs Gordon Conference 2000Associate Institute Director J.

Stuart Nelson, M.D., Ph.D.,served as joint chairman at this year’sGordon Research Conference on “La-sers in Medicine and Biology,” heldJune 10-15 at Connecticut College(New London, Connecticut).

Along with Stefan Andersson-Engels, Ph.D., of the Lund Institute ofPhysics (Lund, Sweden), Nelson or-ganized nine conference sessions fea-turing more than forty handpickedspeakers.

One hundred and fifty researchersand students attended the invitationonly conference which involved, byNelson’s own estimate, more thantwo years of planning.

Conference attendees heard arange of talks covering the most re-cent advances in the field of lasermedicine. Sessions included: “HighResolution Functional Imaging inCells and Tissues: New Methods andContrast Mechanisms” (Bruce J.Tromberg, Ph.D., Chair); “BiomedicalOptics and Laser Treatment of Hu-man Skin” (R. Rox Anderson, M.D.,Chair); “Recent Developments inPhotodynamic Therapy” (Willem M.Star, M.D., Chair); and “Inverse Prob-lems and Statistical Methods in Op-tical Biology” (Thomas Milner, Ph.D.,Chair).

“It’s an honor to serve as chair fora meeting of this magnitude,” says

Nelson. “The Gordon Research Con-ference has long been considered themost important scientific meeting inthe field.” Nelson secured $55,000 infunding from the Whitaker Founda-tion, The National Science Founda-tion, and the U.S. Air Force. “We wereable to fully fund the attendance offorty-eight graduate students andpostdocs, nearly double the numberfunded two years ago.”

Since 1931, Gordon Research Con-ferences have provided an interna-tional forum for the presentation anddiscussion of frontier research in thesciences. GRC sponsored more than100 different conferences during sum-mer 2000. ■

A successful collaborative effortbetween the Beckman Laser In-

stitute and the laboratory of Dr.Nancy Allbritton (Department ofPhysiology and Biophysics at theUniversity of California, Irvine) hasresulted in a new patent for the La-ser Micropipette System (LMS).

The LMS offers a unique methodand apparatus for lysing (dissolving)and analyzing the molecular contentsof a single, living cell or its sub-cel-lular components. By employing itsmicroanalytical capabilities, research-ers can use the LMS to extract a singlecell’s molecular contents, which in-clude DNA, RNA, enzymes, struc-tural proteins, metabolites, drugs,toxins, and physiological reportermolecules. These compounds can

then be isolated for subse-quent analysis.

Marketing plans for theLaser Micropipette Systemare proceeding rapidly. Thedevelopers of the LMS haverecently met with representa-tives at Beckman-Coulter(Fullerton, CA), Eli Lilly (In-dianapolis, IN), and alsoSmithKline Beecham (Phila-delphia, PA) to discuss fur-ther development of thetechnology.

Discussions with thesefirms will continue. In addi-tion, the possibility of spin-ning-off this technology intoa new company is also beingdiscussed. ■

Chris Sims, Ph.D., works intently with the LaserMicropipette System (LMS). The LMS is a newlypatented technology that allows researchers toperform complex, biological microanalyses.

7

(cont’d from page 1)

Newsbriefs(cont’d from p. 4)

‘ODT: GLIMPSING THE SKIN’

Petra Wilder-Smith, D.D.S., Ph.D.,Associate Adjunct Professor of

Surgery, has received major fundingfrom the California Cancer ResearchProgram (California Department ofHealth Services) for her work on non-invasive diagnosis of oral cancer.

The three-year award, which totals$879,000, will support Wilder-Smith’sresearch on the use of photosensitiz-ers (light-sensitive compounds whichcan be applied topically or adminis-tered orally) to detect pre-malignantand malignant lesions of the mouthvia fluorescence.

At present, there is no reliablemethod, with the exception of surgi-cal biopsy, to discriminate between

benign, harmless sores which occurregularly in the mouth and those le-sions which will turn cancerous if leftuntreated.

Reviewers’ comments were enthu-siastic. One reviewer notes, “[This]research has important cancer controlpotential. Development of reliableoral cancer screening technologiescould greatly improve the current re-liance on unassisted visual inspec-tion.”

Institute Director Michael Berns,Ph.D., also has high hopes for theproject. “This research has excep-tional potential, not just for dentistry,but for cancer detection and diagnos-tic medicine in general.” ■

DENTAL PROGRAM EARNS NEW FUNDINGOral Cancer Detection Project Snares $879K

(pre-cancerous) tissue. It can be usedto differentiate between stable andunstable arterial plaque. ODT canalso measure intraocular blood flow,making it possible to diagnose earlydiabetic retinopathy.

Chen and his group are workingwith J. Stuart Nelson, M.D. Ph.D., torefine ODT for dermatological moni-toring. “As we improve our ability toisolate blood flow and structural fea-tures in superficial and deep tissuelayers, we can consider new treat-ments for dermatological disease,malformation, and trauma,” saysChen. “A host of possibilities exist.”

For example, ODT could be usedto monitor blood perfusion and tis-sue viability before, during, and af-ter reconstructive procedures such asskin grafts. “Physicians need a quickand reliable method to test microcir-culation in fresh skin grafts,” Chenexplains. “ODT could provide earlyrecognition of vascular compromise

which would spare patients the riskof additional surgeries.”

ODT also promises to play a ma-jor role in the diagnosis and treatmentof cancer. Clinicians may be able todetect the presence of certain tumorsbased on abnormalities in microvas-culature. In addition, ODT has al-ready been used to monitor changesin blood flow and vessel structurefollowing photodynamic therapy, alaser-based cancer treatment whichutilizes light-sensitive drugs.

In collaboration with G.P. Li,Ph.D., and Mark Bachman, Ph.D., ofUCI’s Department of Electrical Engi-neering, Dr. Chen is also investigat-ing the application of ODT for imagingand measurement of microfluidicflow in micro-electric mechanical sys-tems, also known as “microchips.”

“We’re just getting started,” saysChen. “Speed, resolution, and pen-etration depth can all be improved.This is an exciting development.” ■

PRESIDENTIAL ACCOLADESBLI collaborator Steve George,

M.D., Ph.D., Assistant Professor ofChemical and Biochemical Engineer-ing and Materials Science and an ac-tive faculty member in UCI’s BiomedicalEngineering Program, has been se-lected to receive a Presidential EarlyCareer Award for Scientists and En-gineers (CAREER).

At the behest of the Clinton Ad-ministration, the National ScienceFoundation (NSF) established theCAREER program in 1995 to help sci-entists and engineers in the earlystages of their academic careers todevelop their research and educa-tional programs.

"CAREER awards support excep-tionally promising college and uni-versity junior faculty who are committedto the integration of research andeducation," says NSF Director RitaColwell. "We recognize these facultymembers, new in their careers, asmost likely to become the academicleaders of the 21st Century."

The CAREER Award is the high-est honor bestowed by the U.S. gov-ernment to outstanding scientists andengineers in the early stages of theirindependent research careers. Awardsrange from $200,000 to $500,000 for aperiod of four to five years.

CANCER RESEARCH GRANTPetra Wilder-Smith, D.D.S., Ph.D.,

Associate Adjunct Professor of Sur-gery, has been awarded a $35,000grant by the Cancer Research Foun-dation of America (CRFA) to supportcontinuing research on in vivo fluo-rescence cancer detection as an alter-native to surgical biopsy.

Dr. Wilder-Smith’s project was oneof seventeen research programs

(newsbriefs continued on p. 8)

8

NonprofitOrganizationU.S. Postage

P A I DSanta Ana, CA

Permit No. 1202

Address Service Requested

NEWSBRIEFS

BECKMAN LASER INSTITUTE

1002 Health Sciences Road East

Irvine, California 92612

http://www.bli.uci.edu

J. Stuart Nelson, M.D., Ph.D., (center) has been elected president of the AmericanSociety for Laser Medicine and Surgery. Dr. Nelson, shown here with Ruth Bundy,R.N., Ph.D., and Bruce J. Tromberg, Ph.D., takes office next spring.

(cont’d from page 7)funded by the CRFA (Alexandria,VA) as part of its Innovative ResearchProgram for 2000 (see “DentalProgram Earns New Funding” onpage 7 for more on cancer detectionvia laser excitation and fluorescence).

The CRFA is a non-profit healthfoundation whose mission is theprevention of cancer through researchand education. Since its inception in1985, the CRFA has provided morethan $42.1 mil l ion to over 200scientists working in the field ofcancer prevention and treatment.

MAJOR FUNDING FOR ODTZhongping Chen, Ph.D., Assistant

Professor of Surgery, has receivednew funding from the National Insti-tutes of Health (NIH) for his work onnovel techniques for optical imaging.

The four-year award, worth more than$1 million, will support Dr. Chen’s re-search on Optical Doppler Tomogra-phy (ODT), a light-based imagingmodality which gives clinicians ahigh-resolution glimpse of sub-der-

mal tissue physiology and can simul-taneously provide functional infor-mation such as tumor vasculature(for more on ODT and its applica-tions for medicine, see research up-date on page 4). ■