April 2012Physician NewsAdvanced Multimodality Image-Guided Operating Suite Designed to Enhance Procedures and Enable New InterventionsThe new Advanced Multimodality Image-Guided Operating (AMIGO) suite is astate-of-the-art medical and surgical research environment that facilitates collaboration among multidisciplinary teams of specialists and houses a completearray of advanced imaging equipment and interventional surgical systems.

Continuing Medical Education Page 8Learn about upcoming continuing medical education course offerings from Brigham and Women’s Hospital and Dana-Farber/Brigham and Women’s CancerCenter, through the Harvard Medical School Department of Continuing Education.

Innovative Evaluation and Treatment for Thyroid DiseasesExpert endocrinologists, endocrine surgeons, cytopathologists, ultrasonographers,medical oncologists, and other specialists in the Thyroid Center provide an experienced, multidisciplinary approach to managing thyroid disease.

Mastocytosis Center Offers Advanced Approaches to Diagnosis and TreatmentSpecialists in the Mastocytosis Center have developed advanced approachesto evaluation and treatment of mast cell disease, including state-of-the-arttechniques to accurately diagnose the disease.

Comprehensive Treatment Options for Erectile DysfunctionThe Men’s Sexual Health Clinic provides comprehensive treatment for men with erectile dysfunction, including those who do not benefit from oral phosphodiesterase Type 5 (PDE5) inhibitors.

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2 | Brigham and Women’s Hospital PHYSICIAN NEWS

The new Advanced Multimodality Image-Guided Operating(AMIGO) suite at Brigham and Women’s Hospital (BWH) is astate-of-the-art medical and surgical research environmentthat houses a complete array of advanced imaging equip-ment and interventional surgical systems.To date, more than60 patients have undergone procedures in the AMIGOsuite, which opened in late August 2011.

This innovative operating and imaging research suiteencourages collaboration among multidisciplinary teams ofsurgeons, interventional radiologists, radiation oncologists,imaging physicists, computer scientists, biomedical engi-neers, nurses, and technologists. These teams use AMIGO’sunique equipment array and design to efficiently and precisely guide treatment – before, during, and after the procedure – without the patient or medical team leaving theoperating room.

Brigham and Women’s Hospital is home to a large NationalInstitutes of Health (NIH) grant – the National Center forImage-Guided Therapy (NCIGT). The NCIGT is the NIH’scentral resource for all aspects of research into image-guid-ed procedures, and AMIGO is instrumental to advancingthe mission of the NCIGT — to provide more effectivepatient care.

Physicians use the suite to incorporate research protocolsdesigned to enhance standard clinical procedures and todevelop new therapeutic approaches, including image-

Advanced Multimodality Image-Guided Operating Suite Designed toEnhance Procedures and Enable New Interventions

The nation’s first fully integratedoperating suite to offer immediateintra-procedural access to anextensive range of advanced imagingmodalities, AMIGO’s 5,700-squarefoot space is divided into threeinterconnected procedure roomshousing real-time anatomic, functional, and molecular imagingmodalities, including 3T MRI,PET/CT, fluoroscopy, and ultrasound.

guided craniotomy, MR-guided prostate biopsy for cancerdiagnosis, radiation treatment of prostate cancer and gyne-cological tumors, breast conserving therapy, MR-guidedcryoablation, and brain tumor laser ablation. Using MR temperature mapping to ablate tissue, brain tumor laserablation is a minimally invasive treatment that offers analternative option for patients with metastatic disease in the brain.

“AMIGO represents the latest development in our morethan 20-year history of discovery and innovation in image-guided therapies,” said Ferenc A. Jolesz, MD, Co-PrincipalInvestigator of the National Center for Image-GuidedTherapy at BWH. “Based on our experience in this field, wedesigned this revolutionary new suite with specific capabil-ities to support new image-guided techniques.”

Current procedures in AMIGO include:

• Neurosurgical procedures – Intra-operative MRI-assistedcraniotomy and biopsy, minimally invasive interstitiallaser ablation, endoscopic pituitary surgery, and anteriorskull base surgery;

• MR-guided prostate intervention – biopsy and cancertreatment;

• Brachytherapy for gynecologic and cervical cancers;

• Cryoablation of kidney and liver tumors.

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Future procedures in AMIGO will include the introductionof novel image-guided techniques, including breast cancerlumpectomies, peripheral sarcoma resections, parathyroidresections, percutaneous ablation of bone, soft-tissue andlung tumors, image-guided endoscopic procedures, andcardiac electrophysiology (EP) procedures.

“AMIGO enables clinicians to research, develop, and refinesurgical and interventional techniques that are more focallytargeted to the patient’s disease, are less invasive, andresult in better outcomes,” said Clare Tempany, MD, Co-Principal Investigator of the National Center for Image-Guided Therapy at BWH.

Post-op T2 shows a near grosstotal resection.

This image shows the proximity of thetumor to the motor areas. Close croppedfMRI on T2 show foot, hand, and faceactivations (in purple, blue, and orange),as well as the 3D segmented tumor.

Pre-op DTI shows the tumor sur-rounded by the white mattertracts, including one area wherethe tract goes through part ofthe tumor.

Case Study: MR identifies residual tumor for complete resection

A 43-year-old male golf professional presented with low-grade glioma recurrence in the motor cortex. The originalglioma was resected at BWH in 1999 using intra-operativeMR guidance. Since that time, he has performed well, con-tinuing to work with some intermittent partial seizures. Theteam’s goal was to provide a safe, yet maximal resection ofhis tumor, recognizing the importance of his motor functionto his livelihood. Preoperative structural and functional MRIimages were obtained, as well as diffusion tensor imaging(DTI) with tractography to define the relationship of thetumor to adjacent motor elements, including cortical areasand the cortico-spinal tracts. He underwent an awake cran-iotomy, performed by Alexandra J. Golby, MD, Director,

Image-guided Neurosurgery and Clinical Co-Director ofAMIGO, in the AMIGO suite, which confirmed the findingsof the preoperative functional MRI and tractography withelectrophysiological mapping. After an initial resection, intra-operative MR demonstrated a small area of residual tumor.In addition, intra-operative DTI demonstrated the intra-oper-ative configuration and position of the cortico-spinal tracts.The intra-operative MR images were used to localize thearea of residual tumor and achieve a radiographically com-plete resection. The patient tolerated the procedure welland was discharged on the second postoperative day free ofneurologic deficit.

Intra-operative T2 weighted MRIshows small residual tumor marked inorange with reference to originaltumor size marked in green.

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For More InformationIf you have any questions, or if you would like to tour the new AMIGOsuite, please email InfoBWHAMIGO@partners.org.

The Suite also benefits from other innovative technologiesavailable at BWH, including a Cyclotron to create novel tailored radioactive compounds. Combined with PET/CTimaging, this technology enables clinicians to visualize themetabolically active sites of disease, as well as assess treat-ment efficacy and other disease processes.

4 | Brigham and Women’s Hospital PHYSICIAN NEWS

Comprised of expert endocrinologists, endocrine surgeons,cytopathologists, ultrasonographers, medical oncologists,and other specialists, the multidisciplinary Thyroid Center atBrigham and Women’s Hospital (BWH) is dedicated toimproving outcomes for patients with thyroid diseases.

"Our team provides expert evaluation, treatment, and management for thyroid disease using an experienced, mul-tidisciplinary approach," said P. Reed Larsen, MD, Director,Thyroid Center.

Thyroid Nodule ClinicAmong the largest in the nation, the Center’s ThyroidNodule Clinic, directed by Ellen Marqusee, MD, performs 30-40 diagnostic needle aspirations of thyroid nodulesweekly using ultrasound guidance under the supervision ofCarol B. Benson, MD, Director of Ultrasound, and Peter M.Doubilet, MD, PhD, Senior Vice Chair of Radiology.Cytological evaluation is performed by cytopathologists, led by Edmund S. Cibas, MD, Director, Cytology and FineNeedle Aspiration Center. Overseen by Endocrinologist Erik K. Alexander, MD, a registry of cytopathological resultsof thyroid nodule biopsies of nearly 10,000 patients is main-tained. Nodules found to be benign are monitored periodi-cally by Center specialists for growth or other changes.

Excellent Surgical OutcomesDirected by Francis D. Moore, Jr., MD, Chief, Division ofGeneral and GI Surgery, endocrine surgeons at BWH per-form more than 600 thyroid and thyroid-related procedureseach year and are internationally recognized for the devel-opment of team-driven protocols and checklists that haveinfluenced surgery worldwide. Specifically, the team hasreduced the rate of surgical complications to far belownational averages for recurrent laryngeal nerve injury result-ing in permanent vocal cord paralysis, one percent for bleed-ing, and two percent for parathyroid gland dysfunction.Patients are typically able to return home the same day orthe day following surgery. Upcoming surgical developmentsinclude the use of the Advanced Multimodality Image-Guided Operating (AMIGO) Suite at BWH for select parathy-roid surgery cases.

Follow-up Care and Novel Treatment for Advanced DiseaseWhen indicated, adjuvant radioactive iodine is provided topatients with thyroid cancer. Post-therapy nuclear scanning isused to confirm successful treatment, particularly in patientswith more aggressive disease. Long-term follow up usingsensitive serum thyroglobulin assays is performed to confirmeradication of disease and to diagnose the uncommonrecurrence of disease. Care for patients with advanced thyroid cancer is provided by specialists in the Head andNeck Oncology Center at Dana-Farber/Brigham andWomen’s Cancer Center, under the leadership of Director

Innovative Evaluation and Treatment for Thyroid Diseases

P. Reed Larsen, MDDirector,Thyroid Center

Robert I. Haddad, MD. The Center provides access to novelagents, including the latest clinical trials for thyroid cancer.

Genetic StudiesGenetic developments at the Center include the use ofoncogene screening among patients with thyroid malignan-cy to help predict prognosis. BRAF mutation screening, inparticular, has been shown to be useful among thyroid can-cer patients. Similarly, molecular analysis of cytologically

An ultrasound image of a thyroid nodule (red arrows) in the left thyroidlobe, undergoing fine needle aspiration. The nodule is slightly darker thanthe surrounding normal thyroid tissue, and the 25 gauge needle (yellowarrowheads) is inserted into the nodule to obtain cells to be examined bycytology or for mRNA expression studies.

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Information and ReferralsFor more information, or to refer a patient, please contact ourReferral Coordinators at (617) 732-9894 or emailbwhreferrals@partners.org.

Indications for ReferralThyroid Center specialists generally can provide diagnosticevaluation within two weeks and provide care for:• Thyroid nodules or Goiter;

• Thyroid cancer;

• Hyperthyroidism and hypothyroidism.

brighamandwomens.org • 1-800-MD-TO-BWH | 5

The Mastocytosis Center at Brigham and Women’s Hospital(BWH), a first-of-its-kind center, provides expert multidiscipli-nary evaluation and treatment for patients from across thecountry. Led by Allergist and Immunologist Cem Akin, MD,PhD, specialists in the Center have developed advancedapproaches to diagnosis and treatment of the disease.

“Many cases of mastocytosis are missed, especially early in thedisease, leading to a delay in critical treatment,” said Dr. Akin.“We are collaborating with specialized pathologists and geneti-cists to incorporate innovative approaches designed to ensureaccurate diagnoses.” Center specialists are using a state-of-the-art approach with flow cytometry to detect abnormal mast cellsand also are working with geneticists to screen patients for amutation in the c-kit gene, evident in 95 percent of adult-onsetmastocytosis cases. Genetic screening is performed at the BWHCenter for Advanced Molecular Diagnostics.

Mastocytosis Center Offers Advanced Approaches to Diagnosis and TreatmentDr. Akin and Mariana Castells, MD, PhD, Associate Director,Mastocytosis Center, have authored several papers describingMast Cell Activation Syndrome (MCAS) and the criteria fordiagnosis and treatment (Int Arch Allergy Immunol. 2012;157(3):215-25. and J Allergy Clin Immunol. 2010 Dec;126(6):1099-104.e4.).

Antihistamines, sodium cromolyn, anti-leukotrienes, and epi-nephrine, as well as avoidance of triggers, are used to controlsymptoms. For the 20 percent of patients with mastocytosiswho develop leukemia or aggressive mast cell disease, cytore-ductive therapy is used to destroy mast cells (Blood. 2010 Dec23;116(26):5812-7.). Care for these patients is coordinatedamong specialists in the Center for Hematologic Oncology atDana-Farber/Brigham and Women’s Cancer Center. A newmulticenter trial, led by Daniel J. DeAngelo, MD, PhD, ClinicalDirector, Adult Leukemia Services, Center for HematologicOncology, is using PKC412 to target the mutated c-kit gene inpatients with aggressive mastocytosis with a high degree ofmast cell infiltration in the bone marrow, spleen, or liver. Forchildren with mast cell disease, Center specialists collaboratewith Children’s Hospital Boston.

Cem Akin, MD, PhD,Director, Mastocytosis Center

Access and InformationFor more information, or to refer a patient, please contact our ReferralCoordinator at (617) 732-9894 or bwhreferrals@partners.org.

Indications for ReferralCenter specialists provide specialized evaluation and care forpatients with suspected or confirmed mast cell disease, includ-ing patients with:• Established diagnosis of cutaneous or systemic mastocytosis;• Unexplained recurrent anaphylaxis;• Elevated tryptase, histamine or protaglandins levels;• Severe hypotensive bee sting allergies.

Groundbreaking ResearchResearchers in the Center also are currently leading studiesevaluating its correlation among patients with anaphylaxis orhypotension upon exercising; osteoporosis; or severe beesting allergies.

These studies will help describe the frequency of mast cell dis-ease in particular presentations and better characterize themolecular pathophysiology of mast cell disease. In addition,researchers in the Center are examining familial connections inmast cell disease among families that contain more than onemember with the disease.

“There is a great deal of clinical diversity in mast cell disease,”said Dr. Akin. “Further analysis will likely identify additionalmolecular phenotypes that will help us to develop new treat-ment approaches.”

The Center also has comprehensively studied patients present-ing with mast cell mediators in the blood or urine and relatedsymptoms but no evidence of clonal mast cell disease.

Increased numbers and dense clustering ofmast cells in the bone marrow of a patientwith systemic mastocytosis highlighted bytryptase stain

Normal mast cell

Mariana Castells, MD, PhDAssociate Director, Mastocytosis Center

Daniel J. DeAngelo, MD, PhDClinical Director, Adult Leukemia Services Center for Hematologic Oncology,Dana-Farber/Brigham and Women’s Cancer Center

6 | Brigham and Women’s Hospital PHYSICIAN NEWS

Directed by Urologist Michael P. O’Leary, MD, the Men’sSexual Health Clinic at Brigham and Women’s Hospital pro-vides comprehensive evaluation and treatment for menwith erectile dysfunction (ED).

“Approximately half of men with erectile dysfunction don’tbenefit from oral phosphodiesterase Type 5 (PDE5)inhibitors, presenting a more complex scenario for bothpatients and their physicians,” said Dr. O’Leary. “Whenthese medications aren’t effective, we work with referringphysicians and their patients to present a range of otheroptions.”

Clinic specialists generally determine underlying causes oferectile dysfunction through neurologic testing, hormonalevaluations, and vascular testing. Doppler ultrasound imag-ing is routinely used. Clinic specialists also evaluate andcare for patients with erectile dysfunction due to cancertreatment as part of Dana-Farber/Brigham and Women’sCancer Center.

ED Treatment OptionsFor men who do not respond to PDE5 inhibitors, or whenthese medications are contraindicated, Clinic specialistsoffer numerous alternatives, including:

• Injection therapy – This therapy is highly effective, withabout 80 percent of men responding to treatment andwith few side effects. Patient education and training isrequired for proper use;

Comprehensive Treatment Options for Erectile Dysfunction• Vacuum device – This device uses a manual pump toincrease blood flow and a ring to prevent blood fromdraining before the desired time;

• Penile implant – The Clinic is a high-volume center for thisoption, performing more than 50 implant procedureseach year. This two-piece inflatable device pushes fluidfrom a reservoir into cylinders in the penis. A release valvetransfers fluid back to the reservoir. This option has a highsatisfaction rate among most men and does not requirean abdominal incision. While risk of infection is low(approximately three percent), many Centers do not per-form salvage procedures when infection occurs. Dr.O’Leary is one of few specialists to perform salvage pro-cedures, removing the old device, cleaning the area, andimplanting a new device.

Expert Care for Peyronie’s DiseasePatients with Peyronie’s disease also benefit from penileimplants, and a new treatment that has been approved forDupuytren’s contracture is currently under investigation forPeyronie’s disease. The treatment uses Xiaflex, an enzymetherapy that dissolves excess collagen leading to Peyronie’sdisease and Dupuytren’s contracture. In select cases, surgeryalso may be used to correct Peyronie’s disease.

Information and ReferralsFor more information, or to refer a patient, please contact ourReferral Coordinators at (617) 732-9894 or emailbwhreferrals@partners.org.

Michael P. O’Leary, MDDirector, Men’s Sexual Health Clinic

Access to Brigham and Women’s HospitalPhysician Referral Service(617) 732-9894 or 1-800-MD-TO-BWH (1-800-638-6294)Experienced referral coordinators assist with outpatientappointments, access to our physicians, and informationregarding our specialists and services.

Physician LiaisonPhysician Liaison Ellen Steward provides direct assistancewith patient referrals and consultations with our specialists.Ellen is available to meet with you in person and can bereached at (617) 732-9598, esteward@partners.org, orpager (617) 732-5700, ID #36031.

MD Connect(Inpatient Transfers and Transportation Services)1-877-637-3337

Care Coordination(Facilitation of Care Plan and Discharge Planning)(617) 732-6469

Cardiovascular Access ManagersCardiovascular Access Managers Lisa Downey, MSN, RN,and Gail Jamieson, MSN, RN, assist with inpatient transfersand consultations with our team of cardiovascularexperts. They can be reached at (617) 543-4170.

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Advanced Multimodality Image-Guided Operating Suite Designed to Enhance Procedures and EnableNew Interventions…continued from page 3

Ferenc A. Jolesz, MDCo-Principal Investigator,National Center for Image-Guided Therapy,Brigham and Women’s Hospital

Clare Tempany, MDCo-Principal Investigator,National Center for Image-Guided Therapy,Brigham and Women’s Hospital;Radiologist, Dana-Farber/Brigham and Women’s Cancer Center

Alexandra J. Golby, MDDirector, Image-guided Neurosurgery,Clinical Co-Director, Advanced Multimodality Image-Guided Operating (AMIGO) Suite,Brigham and Women’s Hospital

Akila N. Viswanathan, MD, MPHRadiation Oncologist,Dana-Farber/Brigham and Women’s Cancer Center

Case Study: MR Guides Brachytherapy TreatmentA 67-year-old female (BRCA 1 positive, post hysterectomy,bilateral salpingo-oophorectomy and radical vulvectomy) wasdiagnosed with recurrent vulvar carcinoma. Diagnostic multi-sequence MRI of the pelvis performed before and after 20ccof IV Magnevist showed a 3cm non-circumferential left-sidedthickening of vaginal cuff ending into a nodular oval shapedmass, which was T1 isointense, predominantly T2 isointensewith some T2 hyperintense areas, and demonstrated hetero-geneous enhancement and restriction of diffusion (Image 1).The vaginal component was closely related to the left bladderbase anteriorly in close proximity with the rectum posteriorly.Intra-operative AMIGO MR images were obtained prior toentering the needle-guided interstitial brachytherapy catheterplacement, performed by Radiation Oncologist Akila N.Viswanathan, MD, MPH, in consultation with Dr. Tempany.Imaging sequences consist of gradient-echo, T2-weighted dif-fusion imaging and multiplanar reconstructions.

The preliminary T2W images showed a foley catheter in goodposition (Image 2) and again demonstrate the previouslydescribed 3 cm vaginal mass. Three-dimensional assessmentof this was made prior to the placement of the template andcatheters. The template was then positioned and cathetersinserted and, using real-time MR guidance, was modified andadapted according to the tumor position. Catheters withradioactive seeds were selectively placed in the center of thetumor. The axial and sagittal images were correlated for appro-priate depth and placement of all catheters. The catheterswere kept below the sigmoid colon loop just above the vagi-nal cuff. At the completion of the procedure, all catheters werenoted to be in good position with none located in the sig-moid. The final radiation dose covered the entire tumor(Image 3). Now at six months post procedure, the patientshows no clinical evidence of residual disease.

Image 1

Image 2

Image 3

75 Francis Street, Boston, MA 02115brighamandwomens.org

DEPARTMENT OF CONTINUING EDUCATION

Continuing Medical EducationBrigham and Women’s Hospital and Dana-Farber/Brigham and Women’s Cancer Center are pleased tooffer the following courses, occurring in May 2012,through the Harvard Medical School Department ofContinuing Education. Please call (617) 384-8600 or visitwww.cme.hms.harvard.edu for more information.

8 | Brigham and Women’s Hospital PHYSICIAN NEWS

May 4 – 5An Update and Review of Cardiovascular Disease in WomenLocation: Joseph B. Martin Conference Center,

Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA

Directors: Joanne Foody, MD, FACC, FAHA; Nandita S. Scott, MD, FACC; Malissa J. Wood, MD, FACC, FAHA, FASE

Offered by: Brigham and Women’s Hospital, Department of Medicine; Massachusetts General Hospital, Department of Medicine and Heart Center, Corrigan Women’s Heart Health Program

May 5 Advances in the Treatment of Genitourinary CancersLocation: Dana-Farber Cancer Institute,

450 Brookline Avenue, Boston, MADirectors: Philip W. Kantoff, MD;

Christopher J. Sweeney, MDOffered by: Dana-Farber/Brigham and Women’s

Cancer Center

For more information, or to register for this course, please call (800) 553-3787 or visit dfbwcc.org.

Innovative Evaluation and Treatment forThyroid Diseases…continued from page 4

indeterminate FNA material is provided. In the unusualcircumstance when adequate cytology remains abnormalbut raises the suspicion of malignancy, molecular analysisof thyroid tissue has been shown to more accurately pre-dict benign or malignant disease. This strategy may assistin modifying clinical recommendations to those affectedpatients. The BWH Center for Molecular Diagnostics rou-tinely analyzes cellular material for BRAF, RAS, RET/PTC,and PAX8-PPAR gamma mutations, and further researchcollaborations are underway to allow even broader diag-nostic evidence that nodules are benign.

Thyroid Disease and PregnancyMany thyroid issues first appear or worsen during preg-nancy, and the many pregnant women being followed byobstetricians at BWH have permitted systematic clinicalstudies of these issues. For example, BWH specialistshave helped to establish national guidelines for thyroidhormone treatment during pregnancy. Dr. Alexander leda groundbreaking study published in the New EnglandJournal of Medicine that established guidelines for man-aging thyroid disease during pregnancy. The study foundthat women with hypothyroidism receiving thyroid hormone replacement who became pregnant typicallyrequired a 20 to 40 percent increase in levothyroxinedose to maintain a normal thyroid status in both themother and fetus. Importantly, these results also indicatedthat the increased requirement for thyroid hormonesbegins very early in pregnancy – often by week six orseven.

“These data provide guidance for affected women toreach out to their endocrinogist or primary care physicianimmediately upon a missed menstrual cycle or positivehome pregnancy test – to allow proactive testing andlevothyroxine dose adjustment as soon as possible,” saidDr. Larsen.

Visit our online center for videos featuring surgeries, procedures andGrand Rounds presentations from BWH experts.

MDvideocenter.brighamandwomens.orgNew Online Resource: