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Biology subjects

Shah, B. R.

Publications and source records attributed to Shah, B. R..

7 recordsLinked to original sources
bioRxiv2021

Nitrous Oxide Enhances Focused Ultrasound Mediated Delivery of Viral Gene Therapy

Transcranial Magnetic Resonance Guided Focused Ultrasound (MRgFUS) can be used in conjunction with intravenous microbubbles to open the blood brain barrier (BBB) in discrete brain regions. This method is limited by the microbubble dose, the amount of energy that can be safely delivered across an intact skull, and the inability to target areas of the brain outside of central brain regions. We find that N2O administration substantially decreases the required dose of microbubbles and/or focused ultrasound pressure while still reliably opening the blood brain barrier. Additionally, we observe that the use of nitrous oxide improves the delivery of adeno-associated virus (AAV9) vector when compared to medical air. Our findings may help overcome focused ultrasound limitations and improve targeted delivery of therapeutics in humans. One Sentence SummaryNitrous Oxide potentiates Blood Brain Barrier opening with Focused Ultrasound and enhances viral vector delivery.

neuroscience↗
bioRxiv2021

Single-orientation Quantitative Susceptibility Mapping identifies the Ventral Intermediate Nucleus of the Thalamus

IntroductionThe ventral intermediate nucleus (VIM) represents the primary target in the treatment of tremor. Accurate localization is extremely important given its proximity to other thalamic nuclei. We utilized single orientation quantitative susceptibility mapping (QSM) at 3T to directly visualize the VIM. MethodsFour adult volunteers, one adult cadaver, and an essential tremor patient were scanned on a 3T MRI using a multi-echo gradient echo sequence. QSM images were generated using the improved sparse linear equation and least-squares (iLSQR) algorithm. Two adult subjects underwent multiple head orientation imaging for multi-orientation QSM reconstruction. The VIM was prospectively identified with direct visualization as well as indirect landmark-based localization. ResultsThe bilateral VIM was consistently identified as a hypointense structure within the lateral thalamus, appearing similar on multi-orientation and single-orientation QSM, corresponding to the myelinated dentatorubrothalamic tract (DRTT). The indirect method resulted in a comparatively inferomedial localization, at times missing the VIM and DRTT. ConclusionSingle-orientation QSM offers a clinically feasible, non-invasive imaging-based approach to directly localize the VIM.

neuroscience↗
bioRxiv2020

A Novel Fully Automated MRI-Based Deep Learning Method For Classification Of 1p/19q Co-Deletion Status In Brain Gliomas

BackgroundOne of the most important recent discoveries in brain glioma biology has been the identification of the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status as markers for therapy and prognosis. 1p/19q co-deletion is the defining genomic marker for oligodendrogliomas and confers a better prognosis and treatment response than gliomas without it. Our group has previously developed a highly accurate deep-learning network for determining IDH mutation status using T2-weighted MRI only. The purpose of this study was to develop a similar 1p/19q deep-learning classification network. MethodsMulti-parametric brain MRI and corresponding genomic information were obtained for 368 subjects from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). 1p/19 co-deletions were present in 130 subjects. 238 subjects were non co-deleted. A T2w image only network (1p/19q-net) was developed to perform 1p/19q co-deletion status classification and simultaneous single-label tumor segmentation using 3D-Dense-UNets. Threefold cross-validation was performed to generalize the network performance. ROC analysis was also performed. Dice-scores were computed to determine tumor segmentation accuracy. Results1p/19q-net demonstrated a mean cross validation accuracy of 93.46% across the 3 folds (93.4%, 94.35%, and 92.62%, standard dev=0.8) in predicting 1p/19q co-deletion status with a sensitivity and specificity of 0.90 {+/-}0.003 and 0.95 {+/-}0.01, respectively and a mean AUC of 0.95 {+/-}0.01. The whole tumor segmentation mean Dice-score was 0.80 {+/-} 0.007. ConclusionWe demonstrate high 1p/19q co-deletion classification accuracy using only T2-weighted MR images. This represents an important milestone toward using MRI to predict glioma histology, prognosis, and response to treatment. Keypoints1. 1p/19 co-deletion status is an important genetic marker for gliomas. 2. We developed a non-invasive, MRI based, highly accurate deep-learning method for the determination of 1p/19q co-deletion status that only utilizes T2 weighted MR images IMPORTANCE OF THE STUDYOne of the most important recent discoveries in brain glioma biology has been the identification of the isocitrate dehydrogenase (IDH) mutation and 1p/19q co-deletion status as markers for therapy and prognosis. 1p/19q co-deletion is the defining genomic marker for oligodendrogliomas and confers a better prognosis and treatment response than gliomas without it. Currently, the only reliable way to determine 1p/19q mutation status requires analysis of glioma tissue obtained either via an invasive brain biopsy or following open surgical resection. The ability to non-invasively determine 1p/19q co-deletion status has significant implications in determining therapy and predicting prognosis. We developed a highly accurate, deep learning network that utilizes only T2-weighted MR images and outperforms previously published imagebased methods. The high classification accuracy of our T2w image only network (1p/19q-net) in predicting 1p/19q co-deletion status marks an important step towards image-based stratification of brain gliomas. Imminent clinical translation is feasible because T2-weighted MR imaging is widely available and routinely performed in the assessment of gliomas.

neuroscience↗
bioRxiv2020

Brain Tumor IDH, 1p/19q, and MGMT Molecular Classification Using MRI-based Deep Learning: Effect of Motion and Motion Correction

Deep learning has shown promise for predicting glioma molecular profiles using MR images. Before clinical implementation, ensuring robustness to real-world problems, such as patient motion, is crucial. We sought to evaluate the effects of motion artifact on glioma marker classifier performance and develop a deep learning motion correction network to restore classification accuracies. T2w images and molecular information were retrieved from the TCIA and TCGA databases. Three-fold cross-validation was used to train and test the motion correction network on artifact-corrupted images. We then compared the performance of three glioma marker classifiers (IDH mutation, 1p/19q codeletion, and MGMT methylation) using motion-corrupted and motion-corrected images. Glioma marker classifier performance decreased markedly with increasing motion corruption. Applying motion correction effectively restored classification accuracy for even the most motion-corrupted images. For IDH classification, an accuracy of 99% was achieved, representing a new benchmark in non-invasive image-based IDH classification and exceeding the original performance of the network. Robust motion correction can enable high accuracy in deep learning MRI-based molecular marker classification rivaling tissue-based characterization. STATEMENT OF SIGNIFICANCEDeep learning networks have shown promise for predicting molecular profiles of gliomas using MR images. We demonstrate that patient motion artifact, which is frequently encountered in the clinic, can significantly impair the performance of these algorithms. The application of robust motion correction algorithms can restore the performance of these networks, rivaling tissue-based characterization.

neuroscience↗
bioRxiv2020

MRI-BASED DEEP LEARNING METHOD FOR DETERMINING METHYLATION STATUS OF THE O6 METHYLGUANINE DNA METHYLTRANSFERASE PROMOTER OUTPERFORMS TISSUE BASED METHODS IN BRAIN GLIOMAS

PURPOSEMethylation of the O6-Methylguanine-DNA Methyltransferase (MGMT) promoter results in epigenetic silencing of the MGMT enzyme and confers an improved prognosis and treatment response in gliomas. The purpose of this study was to develop a deep-learning network for determining the methylation status of the MGMT Promoter in gliomas using T2-w magnetic resonance images only. METHODSBrain MRI and corresponding genomic information were obtained for 247 subjects from The Cancer Imaging Archive (TCIA) and The Cancer Genome Atlas (TCGA). 163 subjects had a methylated MGMT promoter. A T2-w image only network (MGMT-net) was developed to determine MGMT promoter methylation status and simultaneous single label tumor segmentation. The network was trained using 3D-Dense-UNets. Three-fold cross-validation was performed to generalize the networks performance. Dice-scores were computed to determine tumor segmentation accuracy. RESULTSMGMT-net demonstrated a mean cross validation accuracy of 94.73% across the 3 folds (95.12%, 93.98%, and 95.12%, standard dev=0.66) in predicting MGMT methylation status with a sensitivity and specificity of 96.31% {+/-}0.04 and 91.66% {+/-}2.06, respectively and a mean AUC of 0.93 {+/-}0.01. The whole tumor segmentation mean Dice-score was 0.82 {+/-} 0.008. CONCLUSIONWe demonstrate high classification accuracy in predicting the methylation status of the MGMT promoter using only T2-w MR images that surpasses the sensitivity, specificity, and accuracy of invasive histological methods such as pyrosequencing, methylation-specific PCR, and immunofluorescence methods. This represents an important milestone toward using MRI to predict glioma histology, prognosis, and response to treatment.

neuroscience↗
bioRxiv2019

Risk factors associated with Avian Influenza subtype H9 outbreaks on poultry farms in Kathmandu valley, Nepal

Poultry sector contributes to four percent in national GDP of Nepal. However, this sector is under threat with periodic outbreaks of Avian Influenza (AI) subtypes H5 and H9 since 2009. This has been both a both public health threat and an economic issue. Since last three years, outbreaks of AI subtype H9 has caused huge economic losses in major poultry producing areas of Nepal. However, the risk factors associated with these outbreaks have not been assessed. A retrospective case-control study was conducted from April 2018 to May 2019 in Kathmandu Valley to understand the risk factors associated with AI subtype H9 outbreaks. Out of 100 farms selected, 50 were \"case\" farms, confirmed positive to H9 at Central Veterinary Laboratory, Kathmandu, and other 50 farms were \"control\" farms, matched for farm size and locality within a radius of three km from the case farm. Each farm was visited to collect information using semi-structured questionnaire. Nineteen potential risk factors were included in the questionnaire under the broad categories: birds and farm characteristics, management aspects and biosecurity status of the farms. Univariable and multivariable logistic regression analysis were conducted to calculate corresponding odds ratios. Identified risk factors associated with AI subtype H9 outbreaks in Kathmandu valley were: \"Birds of age 31-40 days\" (OR= 11.31, 95% CI: 1.31-98.02, p=0.028), \"Older farms operating for >5 years\" (OR= 10.9, 95% CI: 1.76-66.93, p=0.01), \"Commercial layers farms\" (OR=36.0, 95% CI: 0.97-1332.40, p=0.052), \"Used stream water to water birds (OR= 5.7, 95% CI: 1.10-30.13, p=0.039)\", \"Farms without practice of fumigation after each batch of poultry (OR= 4, 95% CI: 1.44-13.13, p=0.009)., \"Farm with previous history of AI (OR= 13.8, 95% CI: 1.34-143.63, p = 0.028), \"Did not applied farm boots (OR= 2.58, 95% CI: 0.98-6.80, p= 0.055), \"Visitors allowed to enter the farms (OR= 2.5, 95% CI: 1.011-6.17, p = 0.047) and \"No foot bath at entry of farms (OR= 3.3, 95% CI: 1.29-8.38, p = 0.013). This study depicts that outbreaks of AI subtype H9 in Kathmandu valley was related to poor management practices and biosecurity in the poultry farms. We suggest improving management practices and increase biosecurity in the farms to reduce incidences of AI subtype H9 outbreaks in Kathmandu valley.

scientific communication and education↗