Papers by Sanjeev Chawla, PhD. DABMP
To distinguish IDH-mutant from IDH wild-type grade-4 astrocytomas, conventional MR imaging (post-... more To distinguish IDH-mutant from IDH wild-type grade-4 astrocytomas, conventional MR imaging (post-contrast T1-weighted and T2-Flair images) was acquired from 57 patients [IDH-mutant (n=23) and IDH-wild-type (n=34) grade-4 astrocytomas]. Post-contrast T1-weighted and T2-FLAIR images were resliced, resampled and co-registered. Neoplasms were segmented into whole tumor, enhancing region, central necrotic region, edema region, and core tumor (contrast enhancing + necrotic region). A total of 105 first-, second-, higher-order and shape based radiomics features were extracted from each ROI. Readily interpretable and quantitative features from different sub-regions of neoplasms were observed with high diagnostic performances in distinguishing IDH-mutant from IDH wild-type grade-4 astrocytomas.
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Clinical Cancer Research, May 9, 2023
The highly aggressive nature of glioblastoma carries a dismal prognosis despite aggressive multim... more The highly aggressive nature of glioblastoma carries a dismal prognosis despite aggressive multimodal therapy. Alternative treatment regimens, such as immunotherapies, are known to intensify the inflammatory response in the treatment field. Follow-up imaging in these scenarios often mimics disease progression on conventional MRI, making accurate evaluation extremely challenging. To this end, revised criteria for assessment of treatment response in high-grade gliomas were successfully proposed by the RANO Working Group to distinguish pseudoprogression from true progression, with intrinsic constraints related to the postcontrast T1-weighted MRI sequence. To address these existing limitations, our group proposes a more objective and quantifiable “treatment agnostic” model, integrating into the RANO criteria advanced multimodal neuroimaging techniques, such as diffusion tensor imaging (DTI), dynamic susceptibility contrast-perfusion weighted imaging (DSC-PWI), dynamic contrast enhanced (DCE)-MRI, MR spectroscopy, and amino acid-based positron emission tomography (PET) imaging tracers, along with artificial intelligence (AI) tools (radiomics, radiogenomics, and radiopathomics) and molecular information to address this complex issue of treatment-related changes versus tumor progression in “real-time”, particularly in the early posttreatment window. Our perspective delineates the potential of incorporating multimodal neuroimaging techniques to improve consistency and automation for the assessment of early treatment response in neuro-oncology.
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Journal of Neurotrauma, Jul 1, 2021
All phase III trials evaluating medical treatments for Traumatic Brain Injury (TBI), performed to... more All phase III trials evaluating medical treatments for Traumatic Brain Injury (TBI), performed to date, have failed. To facilitate future success there is a need for novel outcome metrics that can bridge preclinical studies to clinical proof of concept trials. Our objective was to assess Diffusion Tensor Imaging (DTI) and biofluid-based biomarkers as efficacy outcome metrics in a large animal study evaluating the efficacy of cyclosporine in TBI. This work builds upon our previously published study that demonstrated a reduced volume of injury by 35% with cyclosporine treatment based on magnetic resonance imaging (MRI) results. A focal contusion injury was induced in piglets using a controlled cortical impact (CCI) device. Cyclosporine in a novel cremophor/kolliphor EL-free lipid emulsion, NeuroSTAT, was administered by continuous intravenous infusion for 5 days. The animals underwent DTI on day 5. Glial Fibrillary Acidic Protein (GFAP), as a measure of astroglia injury, and Neurofilament Light (NF-L), as a measure of axonal injury, were measured in blood on day 1, 2 and 5, and in cerebrospinal fluid (CSF) on day 5 post-injury. Normalized fractional anisotropy (FA) was significantly (p=0.027) higher in in the treatment group, indicating preserved tissue integrity with treatment. For the biomarkers, we observed a statistical trend of a decreased level of NF-L in CSF (p=0.051), in the treatment group relative to placebo, indicating less axonal injury. Our findings suggest that DTI, and possibly CSF NF-L, may be feasible as translational endpoints assessing neuroprotective drugs in TBI.
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Frontiers in Neurology, Mar 30, 2022
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Journal of Neuroimaging, Sep 26, 2022
Technological advances in the delivery of radiation and other novel cancer therapies have signifi... more Technological advances in the delivery of radiation and other novel cancer therapies have significantly improved the 5‐year survival rates over the last few decades. Although recent developments have helped to better manage the acute effects of radiation, the late effects such as impairment in cognition continue to remain of concern. Accruing data in the literature have implicated derangements in hemodynamic parameters and metabolic activity of the irradiated normal brain as predictive of cognitive impairment. Multiparametric imaging modalities have allowed us to precisely quantify functional and metabolic information, enhancing the anatomic and morphologic data provided by conventional MRI sequences, thereby contributing as noninvasive imaging‐based biomarkers of radiation‐induced brain injury. In this review, we have elaborated on the mechanisms of radiation‐induced brain injury and discussed several novel imaging modalities, including MR spectroscopy, MR perfusion imaging, functional MR, SPECT, and PET that provide pathophysiological and functional insights into the postradiation brain, and its correlation with radiation dose as well as clinical neurocognitive outcomes. Additionally, we explored some innovative imaging modalities, such as quantitative blood oxygenation level‐dependent imaging, susceptibility‐based oxygenation measurement, and T2‐based oxygenation measurement, that hold promise in delineating the potential mechanisms underlying deleterious neurocognitive changes seen in the postradiation setting. We aim that this comprehensive review of a range of imaging modalities will help elucidate the hemodynamic and metabolic injury mechanisms underlying cognitive impairment in the irradiated normal brain in order to optimize treatment regimens and improve the quality of life for these patients.
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Parasite, Jun 1, 2004
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Journal of Magnetic Resonance Imaging, Mar 19, 2020
Glioblastoma is the most common and most malignant primary brain tumor. Despite aggressive multim... more Glioblastoma is the most common and most malignant primary brain tumor. Despite aggressive multimodal treatment, its prognosis remains poor. Even with continuous developments in MRI, which has provided us with newer insights into the diagnosis and understanding of tumor biology, response assessment in the posttherapy setting remains challenging. We believe that the integration of additional information from advanced neuroimaging techniques can further improve the diagnostic accuracy of conventional MRI. In this article, we review the utility of advanced neuroimaging techniques such as diffusion-weighted imaging, diffusion tensor imaging, perfusion-weighted imaging, proton magnetic resonance spectroscopy, and chemical exchange saturation transfer in characterizing and evaluating treatment response in patients with glioblastoma. We will also discuss the existing challenges and limitations of using these techniques in clinical settings and possible solutions to avoiding pitfalls in study design, data acquisition, and analysis for future studies.
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Critical Care Medicine, 2020
Introduction/Hypothesis: Traumatic brain injury [TBI] is a significant source of morbidity and mo... more Introduction/Hypothesis: Traumatic brain injury [TBI] is a significant source of morbidity and mortality in the United States, with 2.8 million people per year experiencing TBI. TBI accounts for over 50,000 deaths per year, including over 2500 pediatric deaths. We have previously shown that mitochondrial respiration is associated with neurologic outcomes following TBI. A critical regulator of mitochondrial respiration is mitochondrial dynamics (balance of fusion and fission).Following stress, fission can decrease mitochondrial mass and signal apoptosis, while fusion can promote networks and increase oxidative phosphorylation efficiency. We examined changes following focal TBI in a swine model using techniques of Diffusion Tensor Imaging [DTI] MRI to quantify white matter injury and compared it to expression of a key protein involved in fusion, OPA1. We hypothesized that more severe markers of injury measured by DTI would be associated with decreased OPA1 expression Methods: Ten one-month-old piglets were assigned to one of two groups (sham and injury). A moderate to severe cortical contusion was created at the rostral gyrus under anesthesia. Animals were recovered in an intensive care environment and then re-anesthetized 5 days post-TBI for DTI and tissue acquisition. Homogenized tissue from peri-contusional region was homogenized for western blot analysis via iBind method by ThermoFisher Scientific to quantify OPA1 antibody expression, with GAPDH as a normalization protein. DTI looked at mean diffusivity [MD], a marker of tissue edema. Results: An independent-samples t-test was conducted to compare injury vs sham. There was not a significant difference in the brain OPA1 relative density for injury (M= 8566, SD= 3660) and sham (M= 10064, SD= 4795) conditions; p=0.27. Correlation analysis was used to compare OPA1 expression to DTI markers. MD had an inverse correlation with OPA1 expression (r=0.77;p=0.13). Conclusions: MD had an inverse relationship with OPA1 expression in piglets who underwent focal contusion injury indicating a propensity for decreased fusion the more severe the injury. This was supported, although the data was not statistically significant, with a trend towards increased OPA1 expression in sham group compared to injured. Our study suggests that severity of TBI correlates with decreased fusion.
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Molecular Psychiatry, Jan 21, 2021
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Insights Into Imaging, Dec 17, 2022
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Journal of neurosurgery, Jan 3, 2017
OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prog... more OBJECTIVE Mutations in the isocitrate dehydrogenase (IDH) genes are of proven diagnostic and prognostic significance for cerebral gliomas. The objective of this study was to evaluate the clinical feasibility of using a recently described method for determining IDH mutation status by using magnetic resonance spectroscopy (MRS) to detect the presence of 2-hydroxyglutarate (2HG), the metabolic product of the mutant IDH enzyme. METHODS By extending imaging time by 6 minutes, the authors were able to include a point-resolved spectroscopy (PRESS) MRS sequence in their routine glioma imaging protocol. In 30 of 35 patients for whom this revised protocol was used the lesions were subsequently diagnosed histologically as gliomas. Of the remaining 5 patients, 1 had a gangliocytoma, 1 had a primary CNS lymphoma, and 3 had nonneoplastic lesions. Immunohistochemistry and/or polymerase chain reaction were used to detect the presence of IDH mutations in the glioma tissue resected. RESULTS In vivo M...
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NMR in Biomedicine, Mar 15, 2022
Pseudoprogression (PsP) refers to treatment-related clinico-radiologic changes mimicking true pro... more Pseudoprogression (PsP) refers to treatment-related clinico-radiologic changes mimicking true progression (TP) that occurs in patients with glioblastoma (GBM), predominantly within the first 6 months after the completion of surgery and concurrent chemoradiation therapy (CCRT) with temozolomide. Accurate differentiation of TP from PsP is essential for making informed decisions on appropriate therapeutic intervention as well as for prognostication of these patients. Conventional neuroimaging findings are often equivocal in distinguishing between TP and PsP and present a considerable diagnostic dilemma to oncologists and radiologists. These challenges have emphasized the need for developing alternative imaging techniques that may aid in the accurate diagnosis of TP and PsP. In this review, we encapsulate the current state of knowledge in the clinical applications of commonly used metabolic and physiologic magnetic resonance (MR) imaging techniques such as diffusion and perfusion imaging and proton spectroscopy in distinguishing TP from PsP. We also showcase the potential of promising imaging techniques, such as amide proton transfer and amino acid-based positron emission tomography, in providing useful information about the treatment response. Additionally, we highlight the role of “radiomics”, which is an emerging field of radiology that has the potential to change the way in which advanced MR techniques are utilized in assessing treatment response in GBM patients. Finally, we present our institutional experiences and discuss future perspectives on the role of multiparametric MR imaging in identifying PsP in GBM patients treated with “standard-of-care” CCRT as well as novel/targeted therapies.
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The highly aggressive nature of glioblastoma (GBM) leads to a dismal prognosis, and alternative t... more The highly aggressive nature of glioblastoma (GBM) leads to a dismal prognosis, and alternative therapies are being sought. Immunotherapy, such as the Dendritic Cell (DC) vaccine, is currently being evaluated for recurrent GBMs in clinical trials. Follow-up imaging after this immunotherapeutic approach often mimics disease progression on conventional images, making standard MRI evaluation challenging. Our findings indicate that our previously established multiparametric MRI-based prediction model has the capacity to accurately assess response to DC vaccine in recurrent GBM patients, objectively characterizing as either TP or PsP GBM patients, avoiding interruptions in satisfactory treatments, and preventing invasive procedures in PsP cases.
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European Radiology, 2002
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Objectives: To provide a comprehensive view of cortical abnormalities in multiple sclerosis (MS) ... more Objectives: To provide a comprehensive view of cortical abnormalities in multiple sclerosis (MS) including signal, morphological and vascular changes based on high resolution 7T MRI. Background: Histopathological investigation of MS has shown average 25[percnt] of cortical gray matter (GM) is demyelinated in patients with long-standing disease. Despite of recent advances of ultra-high field (eg.7T) MRI which allow markedly improved detection of cortical lesions; detailed inspection of cortical abnormalities in live MS brains is still highly desirable clinically. Methods: Twenty-one clinically confirmed MS patients were scanned on a human 7T MR with a 24-element head array coil. The imaging protocol included high resolution (in plane resolution: 0.23x0.23 mm2, slice thickness=2mm) 2D fast low-angle shot (FLASH) T2*-weighted (T2*w) and T1-weighted, and T2w-FLAIR imaging Results: A total of 31 intracortical lesions were observed corresponding to histopathological type II-IV by Peterson et al (JAMA Neurol 2001). The intracortical lesions differed from white matter (WM) lesions and are characterized by (1) slightly high intensity than surrounding GM, (2) decreased transcortex venules within lesions, (3) well-demarcated either having gyriform shape (n=17) or small plaques (n=10), and (4) inconspicuous sign of “center vein” of lesions (in contrast to WM lesions).The most common intracortical lesion type is subpial lesions (type II-IV). Most WM lesions (WM origin) can be clearly distinctive from cortex. Further, nine patients (43[percnt]) showed subcortical hypointense (dark) rim and band-like abnormalities around cortical ribbon that are likely associated with vascular abnormalities (ie. hemorrhage). Conclusions: 7T MRI shows distinctive patterns (as compared to WM lesions) of intracortical lesions, which may provide in vivo insights into pathogenesis of cortical lesions. The subcortical vascular abnormalities, which are usually not visible at conventional strength MRI, may have important implications of lesion hemorrhagic susceptibility or unfavorable drug effects. Study Supported by: Guthy Jackson Charitable Foundation and Nat’l MS Society. Disclosure: Dr. Ge has nothing to disclose. Dr. Kister has nothing to disclose. Dr. Chawla has nothing to disclose. Dr. Sinnecker has nothing to disclose. Dr. Herbert has received personal compensation for activities with Biogen Idec, Teva, EDM Serono, and Bayer Pharmaceuticals as a consultant. Dr. Paul has received personal compensation for activities with Teva Neuroscience, Sanofi-Aventis Pharmaceuticals, Bayer Schering Pharma, Merck Serono, Biogen Idec, MedImmune, and Novartis., Dr. Wuerfel has nothing to disclose.
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Magnetic Resonance in Medical Sciences, 2011
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Journal of Clinical Ultrasound, Oct 7, 2022
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British Journal of Radiology, Dec 1, 2022
Objectives: To investigate the prognostic utility of DTI and DSC-PWI perfusion-derived parameters... more Objectives: To investigate the prognostic utility of DTI and DSC-PWI perfusion-derived parameters in brain metastases patients. Methods: Retrospective analyses of DTI-derived parameters (MD, FA, CL, CP, and CS) and DSC-perfusion PWI-derived rCBVmax from 101 patients diagnosed with brain metastases prior to treatment were performed. Using semi-automated segmentation, DTI metrics and rCBVmax were quantified from enhancing areas of the dominant metastatic lesion. For each metric, patients were classified as short- and long-term survivors based on analysis of the best coefficient for each parameter and percentile to separate the groups. Kaplan-Meier analysis was used to compare mOS between these groups. Multivariate survival analysis was subsequently conducted. A correlative histopathologic analysis was performed in a subcohort (n = 10) with DTI metrics and rCBVmax on opposite ends of the spectrum. Results: Significant differences in mOS were observed for MDmin (p < 0.05), FA (p < 0.01), CL (p < 0.05), and CP (p < 0.01) and trend toward significance for rCBVmax (p = 0.07) between the two risk groups, in the univariate analysis. On multivariate analysis, the best predictive survival model was comprised of MDmin (p = 0.05), rCBVmax (p < 0.05), RPA (p < 0.0001), and number of lesions (p = 0.07). On histopathology, metastatic tumors showed significant differences in the amount of stroma depending on the combination of DTI metrics and rCBVmax values. Patients with high stromal content demonstrated poorer mOS. Conclusion: Pretreatment DTI-derived parameters, notably MDmin and rCBVmax, are promising imaging markers for prognostication of OS in patients with brain metastases. Stromal cellularity may be a contributing factor to these differences. Advances in knowledge: The correlation of DTI-derived metrics and perfusion MRI with patient outcomes has not been investigated in patients with treatment naïve brain metastasis. DTI and DSC-PWI can aid in therapeutic decision-making by providing additional clinical guidance.
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British Journal of Cancer, Nov 27, 2018
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Papers by Sanjeev Chawla, PhD. DABMP