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Dr. Srinivasan  Mukundan Jr. Md image

Dr. Srinivasan Mukundan Jr. Md

75 Francis St Brigham And Women's Hospital
Boston MA 02115
617 327-7260
Medical School: Other - Unknown
Accepts Medicare: No
Participates In eRX: No
Participates In PQRS: No
Participates In EHR: No
License #: 236798
NPI: 1003902172
Taxonomy Codes:
2085N0700X 2085R0202X

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Publications

Evolution of Movement Disorders Surgery Leading to Contemporary Focused Ultrasound Therapy for Tremor. - Magnetic resonance imaging clinics of North America
Progressively less invasive neurosurgical approaches for the treatment of movement disorders have evolved, beginning with open craniotomy for placement of lesions within pyramidal structures followed by refined stereotactic ablation of extrapyramidal targets that encouraged nondestructive electrode stimulation of deep brain structures. A noninvasive approach using transcranial high-energy focused ultrasound has emerged for the treatment of intractable tremor. The ability to target discreet intracranial sites millimeters in size through the intact skull using focused acoustic energy marks an important milestone in movement disorders surgery. This article describes the evolution of magnetic resonance-guided focused ultrasound for ventrolateral thalamotomy for tremor.Copyright © 2015 Elsevier Inc. All rights reserved.
Pre-operative image-based segmentation of the cranial nerves and blood vessels in microvascular decompression: Can we prevent unnecessary explorations? - Clinical neurology and neurosurgery
This study was conducted to validate the accuracy of image-based pre-operative segmentation using the gold standard endoscopic and microscopic findings for localization and pre-operative diagnosis of the offensive vessel.Fourteen TN and 6 HS cases were randomly selected. All patients had 3T MRI, which included thin-sectioned 3D space T2, 3D Time of Flight and MPRAGE Sequences. Imaging sequences were loaded in BrainLab iPlanNet and fused. Individual segmentation of the affected cranial nerves and the compressing vascular structure was performed by a neurosurgeon, and the results were compared with the microscopic and endoscopic findings by two blinded neurosurgeons. For each case, at least three neurovascular landmarks were targeted. Each segmented neurovascular element was validated by manual placement of the navigation probe over each target, and errors of localization were measured in mm.All patients underwent retro-sigmoid craniotomy and MVD using both microscope and endoscope. Based on image segmentation, the compressing vessel was identified in all cases except one, which was also negative intraoperatively. Perfect correspondence was found between image-based segmentation and endoscopic and microscopic images and videos (Dice coefficient of 1). Measurement accuracy was 0.45±0.21mm (mean±SD).Image-based segmentation is a promising method for pre-operative identification and localization of offending blood vessels causing HFS and TN. Using this method may prevent some unnecessary explorations on especially atypical cases with no vascular contacts. However, negative pre-operative image segmentation may not preclude one from exploration in classic cases of TN or HFS. A multicenter study with larger number of cases is recommended.Copyright © 2015 Elsevier B.V. All rights reserved.
Silicone Implants with Smooth Surfaces Induce Thinner but Denser Fibrotic Capsules Compared to Those with Textured Surfaces in a Rodent Model. - PloS one
Capsular contracture is the most frequent long-term complication after implant-based breast reconstruction or augmentation. The aim of this study was to evaluate the impact of implant surface properties on fibrotic capsule formation in an animal model.Twenty-four rats received 1 scaled down silicone implant each; 12 of the rats received implants with textured surfaces, and the other 12 received implants with smooth surfaces. After 60 and 120 days, rats in each group underwent 7-Tesla Magnetic Resonance Imaging (MRI) and high-resolution ultrasound (HR-US), and specimens of the capsules were acquired and used to measure capsule thickness through histology, collagen density through picro sirius red staining, and analyses of expression of pro-fibrotic and inflammatory genes (Collagen1-4, TGFb1, TGFb3, Smad3, IL4, IL10, IL13, CD68) through qRT-PCR. Furthermore, MRI data were processed to obtain capsule volume and implant surface area.On day 60, histology and HR-US showed that fibrotic capsules were significantly thicker in the textured implant group with respect to the smooth implant group (p<0.05). However, this difference did not persist on day 120 (p=0.56). Capsule thickness decreased significantly over the study period in both smooth and textured implant groups (p<0.05). Thickness measurements were substantiated by MRI analysis and volumes changed accordingly. Implant surface area did not vary between study dates, but it was different between implant types. On day 60, the density of collagen in the fibrotic capsules was significantly lower in the textured implant group with respect to the smooth group (p<0.05), but again this difference did not persist on day 120 (p=0.67). Collagen 1 and CD68 were respectively over- and under expressed in the textured implant group on day 60. Significant differences in the expression of other genes were not observed.Silicone implants with textured surfaces led to temporarily thicker but less dense fibrotic capsules compared with smooth surfaces. 7-Tesla MRI and HR-US are capable for non-invasive in-vivo assessment of capsular fibrosis in an animal model and can provide unique insights into the fibrotic process by 3D reconstruction and surface area measurement.
Craniofacial Measurements of Donors and Recipients Correlate with Aesthetic Outcome in Virtual Face Transplantation. - Plastic and reconstructive surgery. Global open
Face transplantation is an increasingly feasible option for patients with severe disfigurement. Donors and recipients are currently matched based on immune compatibility, skin characteristics, age, and gender. Aesthetic outcomes of the match are not always optimal and not possible to study in actual cases due to ethical and logistical challenges. We have used a reproducible and inexpensive three-dimensional virtual face transplantation (VFT) model to study this issue.Sixty-one VFTs were performed using reconstructed high-resolution computed tomography angiographs of male and female subjects aged 20-69 years. Twenty independent reviewers evaluated the level of disfigurement of the posttransplant models. Absolute differences in 9 soft-tissue measurements and 16 bony cephalometric measurements from each of the VFT donor and recipient pretransplant model pairs were correlated to the reviewers' evaluation of disfigurement after VFT through a multivariate logistic regression model.Five soft-tissue measurements and 3 bony measurements were predictive of the rating of disfigurement after VFT (odds ratio; 95% confidence interval): trichion-to-nasion facial height (1.106; 1.066-1.148), endocanthal width (1.096; 1.051-1.142), exocanthal width (1.067; 1.036-1.099), mouth/chelion width (1.064; 1.019-1.110), subnasale-to-menton facial height (1.029; 1.003-1.056), inner orbit width (1.039; 1.009-1.069), palatal plane/occlusal plane angle (1.148; 1.047-1.258), and sella-nasion/mandibular plane angle (1.079; 1.013-1.150).This study provides early evidence for the importance of soft-tissue and bony measurements in planning of facial transplantation. With future improvements to immunosuppressive regimens and increased donor availability, these measurements may be used as an additional criterion to optimize posttransplant outcomes.
A New Paradigm for Individual Subject Language Mapping: Movie-Watching fMRI. - Journal of neuroimaging : official journal of the American Society of Neuroimaging
Functional MRI (fMRI) based on language tasks has been used in presurgical language mapping in patients with lesions in or near putative language areas. However, if patients have difficulty performing the tasks due to neurological deficits, it leads to unreliable or noninterpretable results. In this study, we investigate the feasibility of using a movie-watching fMRI for language mapping.A 7-minute movie clip with contrasting speech and nonspeech segments was shown to 22 right-handed healthy subjects. Based on all subjects' language functional regions-of-interest, 6 language response areas were defined, within which a language response model (LRM) was derived by extracting the main temporal activation profile. Using a leave-one-out procedure, individuals' language areas were identified as the areas that expressed highly correlated temporal responses with the LRM derived from an independent group of subjects.Compared with an antonym generation task-based fMRI, the movie-watching fMRI generated language maps with more localized activations in the left frontal language area, larger activations in the left temporoparietal language area, and significant activations in their right-hemisphere homologues. Results of 2 brain tumor patients' movie-watching fMRI using the LRM derived from the healthy subjects indicated its ability to map putative language areas; while their task-based fMRI maps were less robust and noisier.These results suggest that it is feasible to use this novel "task-free" paradigm as a complementary tool for fMRI language mapping when patients cannot perform the tasks. Its deployment in more neurosurgical patients and validation against gold-standard techniques need further investigation.Copyright © 2015 by the American Society of Neuroimaging.
Utility of dynamic computed tomography angiography in the preoperative evaluation of skull base tumors. - Journal of neurosurgery
The anatomical complexity of skull base tumors mandates detailed preoperative planning for safe resection. In particular, the location of critical vascular and bony structures can influence the surgical approach. Traditional methods, such as MRI, MR angiography and/or venography (MRA/MRV), CT angiography and/or venography (CTA/CTV), and digital subtraction angiography, each have their limitations. One alternative that combines the benefits of both detailed anatomy compatible with intraoperative image guidance and visualization of the vascular flow is the 320-detector row dynamic volume CTA/CTV. The authors investigated this technique's impact on the surgical approach used in a series of complex intracranial tumors.All patients with complex intracranial tumors who had undergone preoperative dynamic CTA/CTV as well as MRI in the period from July 2010 to June 2012 were retrospectively reviewed. Those in whom only routine CTA/CTV sequences had been obtained were excluded. Clinical records, including imaging studies, operative reports, and hospital course, were reviewed. Ease in detecting specific major arterial and venous tributaries using dynamic CTA/CTV was graded for each case. Furthermore, 2 skull base neurosurgeons projected a desired surgical approach for each tumor based on MRI studies, independent of the CTA/CTV sequences. The projected approach was then compared with the ultimately chosen surgical approach to determine whether preoperative awareness of vasculature patterns altered the actual operative approach.Sixty-four patients were eligible for analysis. Dynamic CTA/CTV successfully demonstrated circle of Willis arteries, major draining sinuses, and deep internal venous drainage in all cases examined. The superior petrosal sinus, vein of Labbé, tentorial veins, and middle fossa veins were also identified in a majority of cases, which played an important role in preoperative planning. Visualization of critical vascular-especially venous-anatomy influenced the surgical approach in 39% (25 of 64) of the cases.Dynamic CTA/CTV has been applied to few neurosurgical disease pathologies to date. This noninvasive technology offers insight into vascular flow patterns as well as 3D anatomical relationships and provides thin-cut sequences for intraoperative navigation. The authors propose dynamic CTA as an addition to the preoperative planning for complex skull base tumors.
"Extraoperative" MRI (eoMRI) for Brain Tumor Surgery: Initial Results at a Single Institution. - World neurosurgery
There is accumulating evidence that extent of resection (EOR) in intrinsic brain tumor surgery prolongs overall survival (OS) and progression-free survival (PFS). One of the strategies to increase EOR is the use of intraoperative MRI (ioMRI); however, considerable infrastructure investment is needed to establish and maintain a sophisticated ioMRI. We report the preliminary results of an extraoperative (eoMRI) protocol, with a focus on safety, feasibility, and EOR in intrinsic brain tumor surgery.Ten patients underwent an eoMRI protocol consisting of surgical resection in a conventional operating room followed by an immediate MRI in a clinical MRI scanner while the patient was still under anesthesia. If findings of the MRI suggested residual safely resectable tumor, the patient was returned to the operating room. A retrospective volumetric analysis was undertaken to investigate the percentage of tumor resected after first resection and if applicable, after further resection.Six of 10 (60%) patients were thought to require no further resection after eoMRI. The EOR in these patients was 97.8% ± 1.8%. In the 4 patients who underwent further resection, the EOR during the original surgery was 88.5% ± 9.5% (P = 0.04). There was an average of 10.1% more tumor removed between the first and second surgery. In 3 of 4 (75%) of patients who returned for further resection, gross total resection of tumor was achieved.An eoMRI protocol appears to be a safe and practical method to ensure maximum safe resections in patients with brain tumors and can be performed readily in all centers with MRI capabilities.Copyright © 2015 Elsevier Inc. All rights reserved.
Histogram analysis of apparent diffusion coefficient within enhancing and nonenhancing tumor volumes in recurrent glioblastoma patients treated with bevacizumab. - Journal of neuro-oncology
While patients with recurrent glioblastoma receiving anti-angiogenic therapy demonstrate significant response rates, the benefit on patient survival is less clear. We assessed whether histogram analysis of diffusion weighted MRI can stratify for progression-free and overall survival. Baseline and 3-6 week post-treatment MRI exams of 91 patients with recurrent glioblastoma treated with bevacizumab were retrospectively evaluated. Histograms of apparent diffusion coefficient (ADC) within the volume of contrast enhancing and nonenhancing T2/FLAIR lesions were analyzed using curve-fit analysis. Overall survival (OS) and progression-free survival (PFS) were assessed using ADC parameters in a Cox proportional hazards model adjusted for clinical variables. Baseline ADC(L)/ADC(M) within nonenhancing T2/FLAIR volume (> or ≤0.64) can stratify OS (HR = 2.24, p = 0.002) and PFS (HR = 1.90, p = 0.005). %ADC(H) within enhancing T1+C volume (> or ≤25 %) can also stratify OS (HR = 0.59, p = 0.034) and PFS (HR = 0.56, p = 0.01). Stratification of patient survival can be improved by merging these two ADC parameters into a single combined ADC factor (HR = 0.17, p < 0.0001). The median OS ratio of patient groups stratified by this combined factor was 2.03, larger than median OS ratio when stratifying by either %ADC(H) within T1+C volume alone (1.3) or ADC(L)/ADC(M) within T2/FLAIR alone (1.86). ADC histogram analysis within both enhancing and nonenhancing components of tumor can be used to stratify for PFS and OS in patients with recurrent glioblastoma.
Recurrent high-grade glioma treated with bevacizumab: prognostic value of MGMT methylation, EGFR status and pretreatment MRI in determining response and survival. - Journal of neuro-oncology
Although bevacizumab represented an important advance in treatment of recurrent high-grade gliomas (HGG), responses occur in fewer than half of patients. There are no validated biomarkers for anti-angiogenic therapy that are available for routine clinical use. We assessed the prognostic values of imaging and molecular markers in this patient population. MRI scans from 191 patients with recurrent HGG obtained prior to initiating bevacizumab were reviewed for areas of enhancement, necrosis, T2/FLAIR abnormality, and ADC values. Serial MRI scans following the initiation of bevacizumab were evaluated for response and progression. Non-radiographic markers including EGFR and MGMT status were also assessed with respect to response and patient survival. 65 of 191 patients (34 %) showed complete or partial response at the time of their best response MRI and demonstrated longer progression free survival (PFS) and overall survival (OS) compared to the group without response (PFS: 6.9 vs 3.5 months, OS: 10.9 vs 6.1 months). Minimum ADC values within enhancing and non-enhancing regions were lower in responders compared to those of non-responders (1,099 vs 984 × 10(-6) mm(2)/s, p = 0.006). Smaller enhancing area was associated with longer OS (HR = 1.99, p = 0.017). The ratio of T2/FLAIR to enhancing area was prognostic of OS for only the Grade III HGG subgroup (HR = 0.14, p = 0.004). Area of enhancing tumor at baseline can stratify survival in patients with recurrent HGG treated with bevacizumab. The extent of edema relative to enhancing area may have a prognostic role specific to Grade III HGG.
Facial appearance transfer and persistence after three-dimensional virtual face transplantation. - Plastic and reconstructive surgery
Facial appearance transfer from donor to recipient in face transplantation is a concern. Previous studies of facial appearance transfer and facial appearance persistence (preservation of the recipient's facial likeness) in face transplants simulated using two-dimensional photographic manipulations found low facial appearance transfer (2.6 percent) and high facial appearance persistence (66 percent). Three-dimensional computer simulation of complex facial transplant patterns may improve the accuracy of facial appearance transfer and facial appearance persistence estimations.Three-dimensional virtual models of human faces were generated from deidentified computed tomographic angiographs and used as "donors" or "recipients" for virtual face transplantation. Surgical planning software was used to perform 73 virtual face transplantations by creating specific facial defects (mandibular, midface, or large) in the recipient models and restoring them with allografts extracted from the donor models. Twenty independent reviewers evaluated the resemblance of each resulting posttransplant model to the donor (facial appearance transfer) and recipient (facial appearance persistence). The results were analyzed using tests for equal results with one-sample and pairwise Rao-Scott Pearson chi-square testing, correcting for clustering and multiple testing.Overall rates of facial appearance persistence and facial appearance transfer were high (69.2 percent) and low (32.4 percent), respectively. The mandibular pattern had the highest rates of facial appearance persistence and lowest rates of facial appearance transfer. Facial appearance persistence and transfer were similar across sexes.Facial appearance persistence is high and facial appearance transfer is low after virtual face transplantation. Appearance transfer and persistence after virtual face transplantation are more dependent on the anatomy than on the size of transplanted facial aesthetic units. This information may reassure recipients of partial face transplants and donor families.

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