In Vivo Imaging of Neuroinflammatory Targets in Treatment-Resistant Epilepsy

Sharma, Ayushe A.; Szaflarski, Jerzy P.

doi:10.1007/s11910-020-1025-9

Cited by 17 publications

(25 citation statements)

References 135 publications

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“…For example, as demonstrated by findings from studies of animal models of epilepsy and resected human epileptic tissue, sustained neuroinflammation causes chronic hyperexcitability, lower seizure threshold, and neuronal death (Aronica et al, 2010;Maroso et al, 2010;Ravizza et al, 2011;Vezzani and Friedman, 2011;Vezzani et al, 2019). A neuroimaging-based biomarker of neuroinflammation may allow tracking disease progression, treatment response, and associated comorbidities and cognitive impairments; such a tool may even identify a way to prevent these phenomena in the first place (Sharma and Szaflarski, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Surgical planning is straightforward in patients with sMRI-detectable lesions, but challenging in the 20-30% patients who are MR-negative (Salmenpera et al, 2007;Jobst and Cascino, 2015;Muhlhofer et al, 2017). Moreover, patients with sMRI-detectable lesions experience 2.5-2.9 times better surgical outcomes than those with normal sMRIs (Salmenpera et al, 2007;Giorgio and De Stefano, 2010;Téllez-Zenteno et al, 2010;Finke, 2018;Alberts et al, 2020;Sharma and Szaflarski, 2020). Despite sMRI's capacity to pinpoint major structural abnormalities (e.g., large ischemic lesions), the data demonstrate its diminished sensitivity and specificity for detecting the smaller, more focalized neuroinflammatory phenomena (Barr Abbreviations: MRSI, Magnetic resonance spectroscopic imaging; MRSI-t, MRSIbased brain temperature; ROI(s), Region(s) of interest; COVrep, Coefficient of variation for repeated measures; SEM, Standard error of measurement; MDC, Minimal Detectable Change; T CRE , MRSI-based brain temperature calculated according to the equation T CRE = −102.…”

Section: Introductionmentioning

confidence: 99%

“…61( H20−CRE ) + 206.1 • C; tCre, creatine + phosphocreatine (total creatine); tCho, total choline; NAA, N-acetylaspartate; Glx, combined signal from glutamine and glutamate; MI, myo-inositol. Kälviäinen and Salmenperä, 2002;Blümcke et al, 2012;Sharma and Szaflarski, 2020). Therefore, there is a need to identify a sensitive and specific in vivo biomarker of neuroinflammatory pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

“…Other currently available approaches are invasive and/or costly (e.g., lumbar puncture, positron emission tomography [PET]). Further, PET relies on the use of radioisotopes that may localize key neuroinflammatory cells, but variable quantitative accuracy, limited bioavailability, and unclear specificity of ligand-target binding are critical gaps that limit its clinical utility (Vivash and OBrien, 2016;Best et al, 2019;Dickstein et al, 2019;Ghadery et al, 2019;Hamelin et al, 2019;Sharma and Szaflarski, 2020). Thus, the question remains: how can we non-invasively localize neuroinflammation in a living human brain?…”

Section: Introductionmentioning

confidence: 99%

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Repeatability and Reproducibility of in-vivo Brain Temperature Measurements

Sharma

Nenert

Mueller

et al. 2020

Front. Hum. Neurosci.

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Background: Magnetic resonance spectroscopic imaging (MRSI) is a neuroimaging technique that may be useful for non-invasive mapping of brain temperature (i.e., thermometry) over a large brain volume. To date, intra-subject reproducibility of MRSI-based brain temperature (MRSI-t) has not been investigated. The objective of this repeated measures MRSI-t study was to establish intra-subject reproducibility and repeatability of brain temperature, as well as typical brain temperature range.Methods: Healthy participants aged 23–46 years (N = 18; 7 females) were scanned at two time points ~12-weeks apart. Volumetric MRSI data were processed by reconstructing metabolite and water images using parametric spectral analysis. Brain temperature was derived using the frequency difference between water and creatine (TCRE) for 47 regions of interest (ROIs) delineated by the modified Automated Anatomical Labeling (AAL) atlas. Reproducibility was measured using the coefficient of variation for repeated measures (COVrep), and repeatability was determined using the standard error of measurement (SEM). For each region, the upper and lower bounds of Minimal Detectable Change (MDC) were established to characterize the typical range of TCRE values.Results: The mean global brain temperature over all subjects was 37.2°C with spatial variations across ROIs. There was a significant main effect for time [F(1, 1,591) = 37.0, p < 0.0001] and for brain region [F(46, 1,591) = 2.66, p < 0.0001]. The time*brain region interaction was not significant [F(46, 1,591) = 0.80, p = 0.83]. Participants' TCRE was stable for each ROI across both time points, with ROIs' COVrep ranging from 0.81 to 3.08% (mean COVrep = 1.92%); majority of ROIs had a COVrep <2.0%.Conclusions: Brain temperature measurements were highly consistent between both time points, indicating high reproducibility and repeatability of MRSI-t. MRSI-t may be a promising diagnostic, prognostic, and therapeutic tool for non-invasively monitoring brain temperature changes in health and disease. However, further studies of healthy participants with larger sample size(s) and numerous repeated acquisitions are imperative for establishing a reference range of typical brain TCRE, as well as the threshold above which TCRE is likely pathological.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Repeatability and Reproducibility of in-vivo Brain Temperature Measurements

Sharma

Nenert

Mueller

et al. 2020

Front. Hum. Neurosci.

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“…None of these tools alone has the needed sensitivity and specificity for localizing SOZ. Building a hypothesis about the SOZ based on the concordance between these tests' results is key to achieving a favorable surgical outcome [ 10 ]. DRE patients with detectable MRI lesions are 2.5-2.9 times more likely to experience a favorable surgical outcome [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Use of Innovative SPECT Techniques in the Presurgical Evaluation of Patients with Nonlesional Extratemporal Drug-Resistant Epilepsy

et al. 2021

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Up to 30% of patients with epilepsy may not respond to antiepileptic drugs. Patients with drug-resistant epilepsy (DRE) should undergo evaluation for seizure onset zone (SOZ) localization to consider surgical treatment. Cases of drug-resistant nonlesional extratemporal lobe epilepsy (ETLE) pose the biggest challenge in localizing the SOZ and require multiple noninvasive diagnostic investigations before planning the intracranial monitoring (ICM) or direct resection. Ictal Single Photon Emission Computed Tomography (i-SPECT) is a unique functional diagnostic tool that assesses the SOZ using the localized hyperperfusion that occurs early in the seizure. Subtraction ictal SPECT coregistered to MRI (SISCOM), statistical ictal SPECT coregistered to MRI (STATISCOM), and PET interictal subtracted ictal SPECT coregistered with MRI (PISCOM) are innovative SPECT methods for the determination of the SOZ. This article comprehensively reviews SPECT and sheds light on its vital role in the presurgical evaluation of the nonlesional extratemporal DRE.

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An exploratory study of brain temperature and choline abnormalities in temporal lobe epilepsy patients with depressive symptoms

Oates,

Sharma,

Nenert

et al. 2023

Epilepsia Open

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ObjectiveEpilepsy and depression share neurobiological origins, and evidence suggests a possible bidirectional relationship that remains poorly understood. This exploratory, cross‐sectional study aimed to investigate this relationship by employing magnetic resonance spectroscopic imaging (MRSI) and thermometry (MRSI‐t) in patients with temporal lobe epilepsy (TLE) with comorbid depressive symptoms and control participants. This is the first study to combine MRSI and MRSI‐t to examine brain temperature and choline abnormalities in regions implicated in seizure onset and depression.MethodsTwenty‐six patients with TLE and 26 controls completed questionnaires and underwent imaging at 3T. Volumetric echo‐planar MRSI/MRSI‐t data were processed within the Metabolite Imaging and Data Analysis System (MIDAS). Choline (CHO) was quantified as a ratio over creatine (CRE; CHO/CRE). Brain temperature (TCRE) was calculated based on the chemical shift difference of H2O relative to CRE's stable location on the ppm spectrum. The Hospital Anxiety and Depression Scale measured anxiety and depressive symptoms. The Chalfont Seizure Severity Scale measured seizure severity in patients with TLE. Two sets of voxelwise independent sample t tests examined group differences in CHO/CRE and TCRE maps. Voxel‐based multimodal canonical correlation analysis (mCCA) linked both datasets to investigate if, how, and where CHO/CRE and TCRE abnormalities were correlated in TLE participants and controls.ResultsCompared to controls, patients with TLE reported more depressive symptoms (P = 0.04) and showed CHO/CRE and TCRE elevations in left temporal and bilateral frontal regions implicated in seizure onset and depressive disorders (pFWE < 0.05). For the TLE group, CHO/CRE levels in temporal and frontal cortices were associated with elevated TCRE in bilateral frontal and temporal gyri (r = 0.96), and decreased TCRE in bilateral fronto‐parietal regions (r = −0.95).SignificanceAbnormalities in TCRE and CHO/CRE were observed in seizure‐producing areas and in regions implicated in depression. These preliminary findings suggest that common metabolic changes may underlie TLE and depression. Our results suggest further investigations into the proposed bidirectional mechanisms underlying this relationship are warranted.

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In Vivo Imaging of Neuroinflammatory Targets in Treatment-Resistant Epilepsy

Cited by 17 publications

References 135 publications

Repeatability and Reproducibility of in-vivo Brain Temperature Measurements

Repeatability and Reproducibility of in-vivo Brain Temperature Measurements

Use of Innovative SPECT Techniques in the Presurgical Evaluation of Patients with Nonlesional Extratemporal Drug-Resistant Epilepsy

An exploratory study of brain temperature and choline abnormalities in temporal lobe epilepsy patients with depressive symptoms

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