The objective of our study was to predict response to chemoradiation therapy in patients with head and neck squamous cell carcinoma (HNSCC) by combined use of diffusion-weighted imaging (DWI) and ...high-spatial-resolution, high-temporal-resolution dynamic contrast-enhanced MRI (DCE-MRI) parameters from primary tumors and metastatic nodes.
Thirty-two patients underwent pretreatment DWI and DCE-MRI using a modified radial imaging sequence. Postprocessing of data included motion-correction algorithms to reduce motion artifacts. The median apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), extracellular extravascular volume fraction (v(e)), and plasma volume fraction (v(p)) were computed from primary tumors and nodal masses. The quality of the DCE-MRI maps was estimated using a threshold median chi-square value of 0.10 or less. Multivariate logistic regression and receiver operating characteristic curve analyses were used to determine the best model to discriminate responders from nonresponders.
Acceptable χ(2) values were observed from 84% of primary tumors and 100% of nodal masses. Five patients with unsatisfactory DCE-MRI data were excluded and DCE-MRI data for three patients who died of unrelated causes were censored from analysis. The median follow-up for the remaining patients (n = 24) was 23.72 months. When ADC and DCE-MRI parameters (K(trans), v(e), v(p)) from both primary tumors and nodal masses were incorporated into multivariate logistic regression analyses, a considerably higher discriminative accuracy (area under the curve AUC = 0.85) with a sensitivity of 81.3% and specificity of 75% was observed in differentiating responders (n = 16) from nonresponders (n = 8).
The combined use of DWI and DCE-MRI parameters from both primary tumors and nodal masses may aid in prediction of response to chemoradiation therapy in patients with HNSCC.
Glioblastoma (GBM) is the most malignant brain tumor in adults, with a dismal prognosis despite aggressive multi-modal therapy. Immunotherapy is currently being evaluated as an alternate treatment ...modality for recurrent GBMs in clinical trials. These immunotherapeutic approaches harness the patient's immune response to fight and eliminate tumor cells. Standard MR imaging is not adequate for response assessment to immunotherapy in GBM patients even after using refined response assessment criteria secondary to amplified immune response. Thus, there is an urgent need for the development of effective and alternative neuroimaging techniques for accurate response assessment. To this end, some groups have reported the potential of diffusion and perfusion MR imaging and amino acid-based positron emission tomography techniques in evaluating treatment response to different immunotherapeutic regimens in GBMs. The main goal of these techniques is to provide definitive metrics of treatment response at earlier time points for making informed decisions on future therapeutic interventions. This review provides an overview of available immunotherapeutic approaches used to treat GBMs. It discusses the limitations of conventional imaging and potential utilities of physiologic imaging techniques in the response assessment to immunotherapies. It also describes challenges associated with these imaging methods and potential solutions to avoid them.
Pathophysiology of multiple sclerosis (MS) lesions is dynamic and changes over time. The purpose of this exploratory study was to determine the longitudinal changes in MS lesions over time on ...ultra-high field MR imaging. Nine patients with MS underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo-T2*-weighted imaging on 7T MRI at baseline and after ~2.4 years of follow-up. Morphologic imaging characteristics, signal intensity patterns and quantitative susceptibility mapping (QSM) values of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on T2*-weighted images and/or SWI as well as hyperintense signal on QSM. Lesions were considered "non-iron-laden" if they were hyperintense on T2*/SWI and isointense or hyperintense on QSM. Total of 162 non-iron-laden and 29 iron-laden lesions were observed at baseline. No change in baseline lesion size during follow up was recorded in 92.7%; no change in lesion-vessel relationship in 86.5%; and no change in signal intensity pattern in 96.9% of lesions. Three lesions which were non-iron-laden at baseline, exhibited iron at follow-up. In two iron-laden lesions, redistribution of iron content was observed at follow-up. Two-thirds of these iron-laden lesions showed an increase in QSM at follow-up relative to baseline, and the remaining one-third exhibited decrease in QSM. Most of the newly formed lesions (11/13, 84.6%) at follow-up were iron-laden. 7T multiparametric MRI is a useful tool for tracking the evolution of MS lesions, especially with regard to changes in iron content.
Abstract
Attention-deficit hyperactivity disorder (ADHD) is a neurological and neurodevelopmental childhood-onset disorder characterized by a persistent pattern of inattentiveness, impulsiveness, ...restlessness, and hyperactivity. These symptoms may continue in 55–66% of cases from childhood into adulthood. Even though the precise etiology of ADHD is not fully understood, it is considered as a multifactorial and heterogeneous disorder with several contributing factors such as heritability, auxiliary to neurodevelopmental issues, severe brain injuries, neuroinflammation, consanguineous marriages, premature birth, and exposure to environmental toxins. Neuroimaging and neurodevelopmental assessments may help to explore the possible role of genetic variations on ADHD neuropsychobiology. Multiple genetic studies have observed a strong genetic association with various aspects of neuropsychobiological functions, including neural abnormalities and delayed neurodevelopment in ADHD. The advancement in neuroimaging and molecular genomics offers the opportunity to analyze the impact of genetic variations alongside its dysregulated pathways on structural and functional derived brain imaging phenotypes in various neurological and psychiatric disorders, including ADHD. Recently, neuroimaging genomic studies observed a significant association of brain imaging phenotypes with genetic susceptibility in ADHD. Integrating the neuroimaging-derived phenotypes with genomics deciphers various neurobiological pathways that can be leveraged for the development of novel clinical biomarkers, new treatment modalities as well as therapeutic interventions for ADHD patients. In this review, we discuss the neurobiology of ADHD with particular emphasis on structural and functional changes in the ADHD brain and their interactions with complex genomic variations utilizing imaging genetics methodologies. We also highlight the genetic variants supposedly allied with the development of ADHD and how these, in turn, may affect the brain circuit function and related behaviors. In addition to reviewing imaging genetic studies, we also examine the need for complementary approaches at various levels of biological complexity and emphasize the importance of combining and integrating results to explore biological pathways involved in ADHD disorder. These approaches include animal models, computational biology, bioinformatics analyses, and multimodal imaging genetics studies.
Machine learning (ML) integrated with medical imaging has introduced new perspectives in precision diagnostics of high-grade gliomas, through radiomics and radiogenomics. This has raised hopes for ...characterizing noninvasive and in vivo biomarkers for prediction of patient survival, tumor recurrence, and genomics and therefore encouraging treatments tailored to individualized needs. Characterization of tumor infiltration based on pre-operative multi-parametric magnetic resonance imaging (MP-MRI) scans may allow prediction of the loci of future tumor recurrence and thereby aid in planning the course of treatment for the patients, such as optimizing the extent of resection and the dose and target area of radiation. Imaging signatures of tumor genomics can help in identifying the patients who benefit from certain targeted therapies. Specifying molecular properties of gliomas and prediction of their changes over time and with treatment would allow optimization of treatment. In this article, we provide neuro-oncology, neuropathology, and computational perspectives on the promise of radiomics and radiogenomics for allowing personalized treatments of patients with gliomas and discuss the challenges and limitations of these methods in multi-institutional clinical trials and suggestions to mitigate the issues and the future directions.
Intravascular injection of certain adeno-associated virus vector serotypes can cross the blood-brain barrier to deliver a gene into the CNS. However, gene distribution has been much more limited ...within the brains of large animals compared to rodents, rendering this approach suboptimal for treatment of the global brain lesions present in most human neurogenetic diseases. The most commonly used serotype in animal and human studies is 9, which also has the property of being transported via axonal pathways to distal neurons. A small number of other serotypes share this property, three of which were tested intravenously in mice compared to 9. Serotype hu.11 transduced fewer cells in the brain than 9, rh8 was similar to 9, but hu.32 mediated substantially greater transduction than the others throughout the mouse brain. To evaluate the potential for therapeutic application of the hu.32 serotype in a gyrencephalic brain of larger mammals, a hu.32 vector expressing the green fluorescent protein reporter gene was evaluated in the cat. Transduction was widely distributed in the cat brain, including in the cerebral cortex, an important target since mental retardation is an important component of many of the human neurogenetic diseases. The therapeutic potential of a hu.32 serotype vector was evaluated in the cat homologue of the human lysosomal storage disease alpha-mannosidosis, which has globally distributed lysosomal storage lesions in the brain. Treated alpha-mannosidosis cats had reduced severity of neurological signs and extended life spans compared to untreated cats. The extent of therapy was dose dependent and intra-arterial injection was more effective than intravenous delivery. Pre-mortem, non-invasive magnetic resonance spectroscopy and diffusion tensor imaging detected differences between the low and high doses, and showed normalization of grey and white matter imaging parameters at the higher dose. The imaging analysis was corroborated by post-mortem histological analysis, which showed reversal of histopathology throughout the brain with the high dose, intra-arterial treatment. The hu.32 serotype would appear to provide a significant advantage for effective treatment of the gyrencephalic brain by systemic adeno-associated virus delivery in human neurological diseases with widespread brain lesions.
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