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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.

Head and neck squamous cell carcinoma (HNSCC) is a very aggressive disease with a poor prognosis for advanced-stage tumors. Recent clinical, genomic, and cellular studies have revealed the highly heterogeneous and immunosuppressive nature of HNSCC. Despite significant advances in multimodal therapeutic interventions, failure to cure and recurrence are common and account for most deaths. It is becoming increasingly apparent that tumor microenvironment (TME) plays a critical role in HNSCC tumorigenesis, promotes the evolution of aggressive tumors and resistance to therapy, and thereby adversely affects the prognosis. A complete understanding of the TME factors, together with the highly complex tumor-stromal interactions, can lead to new therapeutic interventions in HNSCC. Interestingly, different molecular and immune landscapes between HPV +ve and HPV -ve (human papillomavirus) HNSCC tumors offer new opportunities for developing individualized, targeted chemoimmunotherapy (CIT) regimen. This review highlights the current understanding of the complexity between HPV +ve and HPV -ve HNSCC TME and various tumor-stromal cross-talk modulating processes, including epithelial-mesenchymal transition (EMT), anoikis resistance, angiogenesis, immune surveillance, metastatic niche, therapeutic resistance, and development of an aggressive tumor phenotype. Furthermore, we summarize the recent developments and the rationale behind CIT strategies and their clinical applications in HPV +ve and HPV -ve HNSCC.

Autism spectrum disorder (ASD) is a neurological and developmental disorder characterized by social impairment and restricted interactive and communicative behaviors. It may occur as an isolated disorder or in the context of other neurological, psychiatric, developmental, and genetic disorders. Due to rapid developments in genomics and imaging technologies, imaging genetics studies of ASD have evolved in the last few years. Increased risk for ASD diagnosis is found to be related to many specific single-nucleotide polymorphisms, and the study of genetic mechanisms and noninvasive imaging has opened various approaches that can help diagnose ASD at the nascent level. Identifying risk genes related to structural and functional changes in the brain of ASD patients provide a better understanding of the disease's neuropsychiatry and can help identify targets for therapeutic intervention that could be useful for the clinical management of ASD patients.

Purpose: Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD + ) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a 1 H MRS pulse sequence for the in vivo, localized 1 H MRS detection of NAD + from the human brain., Methods: Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD + quantification was measured in 11 healthy volunteers. The association of cerebral NAD + with age was assessed in 16 healthy subjects 26-78 years old., Results: Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H 2 , H 4 , and H 6 protons of the nicotinamide moiety of NAD + between 8.9-9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age-dependent decline of the NAD + levels in the brain was also observed (β = -1.24 μM/y, SE = 0.21, P < 0.001)., Conclusion: We demonstrated the feasibility and robustness of a newly developed 1 H MRS technique to measure localized cerebral NAD + at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD + from different regions of the brain as well as from other tissues., (© 2019 International Society for Magnetic Resonance in Medicine.)

Quantitative mapping of the in vivo dynamics of cellular metabolism via non-invasive imaging contributes to our understanding of the initiation and progression of diseases associated with dysregulated metabolic processes. Current methods for imaging cellular metabolism are limited by low sensitivities, costs or the use of specialized hardware. Here, we introduce a method that captures the turnover of cellular metabolites by quantifying signal reductions in proton magnetic resonance spectroscopy (MRS) resulting from the replacement of 1 H with 2 H. The method, which we termed quantitative exchanged-label turnover MRS, only requires deuterium-labelled glucose and standard magnetic resonance imaging scanners, and with a single acquisition provides steady-state information and metabolic rates for several metabolites. We used the method to monitor glutamate, glutamine, γ-aminobutyric acid and lactate in the brains of unaffected and glioma-bearing rats following the administration of 2 H 2 -labelled glucose and 2 H 3 -labelled acetate. Quantitative exchanged-label turnover MRS should broaden the applications of routine 1 H MRS.

Head and neck squamous cell carcinomas (HNSCCs) are a group of heterogeneous aggressive tumors affecting more than half a million patients worldwide annually. While the tobacco- and alcohol-associated HNSCC tumors are declining, human papillomavirus (HPV)-induced tumors are on rise. Despite recent advances in multimodality therapeutic interventions including surgery in combination with chemoradiation therapy (CRT), the overall 5-year survival has not improved more than 50%. The underlying reasons for this dismal prognosis is the intrinsic or acquired resistance to CRT. While previous studies were focused to target tumor cells, recent findings have implicated the involvement of tumor microenvironment (TME) on tumor progression and response to therapy. HNSCC TME includes cancer-associated fibroblasts (CAFs), endothelial cells, immune cells, endocrine cells, and the extracellular matrix (ECM) proteins including collagen and fibronectin. Understanding the crosstalk between TME and cancer cells is important to formulate more effective novel therapies and to overcome resistance mechanisms. Here, we summarized the current literature on recent advances on HNSCC TME with special emphasis on novel cell-cell interactions and therapies currently under development.

Noninvasive imaging of functional and molecular changes in cancer has become an indispensable tool for studying cancer in vivo. Targeting the functional and molecular changes in cancer imaging provides a platform for the in vivo analysis of the mechanisms such as gene expression, signal transduction, biochemical reactions, regulatory pathways, cell trafficking, and drug action underlying cancer noninvasively. The main focus of imaging in cancer is the development of new contrast methods/molecular probes for the early diagnosis and the precise evaluation of therapy response. In clinical setup, imaging modalities facilitate screening, prediction, staging, biopsy and therapy guidance, therapy response, therapy planning, and prognosis of cancer. In this book chapter, we review different established and emerging in vivo imaging modalities and their applications in monitoring functional, molecular, and metabolic changes in cancer.

Portal vein thrombosis (PVT) is thrombosis of the portal -circulation, which may present with varied symptoms. However, increased use of abdominal imaging has noted a large number of incidental PVT. At the same time, PVT may be overlooked in the absence of the characteristic symptoms. More recently, a JAK2 mutation has been recognised as a cause of PVT. Anticoagulation is the mainstay of treatment, but can pose a dilemma because of the associated coagulopathy, the presence of varices and thrombocytopenia., (© Royal College of Physicians 2017. All rights reserved.)

A few studies have reported that magnetization transfer (MT) -preparation interacts with blood oxygen level dependent (BOLD) contrast used for functional magnetic resonance imaging (MRI). However, the mechanism is still not well established. This study shows that blood oxygenation level itself affects MT contrast. MT ratio (MTR) decreases with increased blood oxygenation, which is demonstrated by ex vivo and in vivo experiments. Oxygenated blood shows less MTR contrast compared to deoxygenated blood sample; and higher levels of oxygen inhalation decrease tissue MTR in vivo especially in brain tumor region. The percentage reduction of MTR due to hyperoxia inhalation, referred to as the blood oxygen dependent magnetization transfer (BOLDMT) effect, correlates well with tissue oxygen extraction, which is highest in well-vascularized tumor rim, followed by inner tumor, gray matter (GM), and white matter (WM) normal tissue. Simulations and experiments demonstrate that BOLDMT effect induced with hyperoxia inhalation may be generated by decreased tissue T (1) due to increased O(2) dissolution and increased tissue T (2) due to reduced deoxyhemoglobin (dHb) concentration. Compared to regular T (2)* weighted BOLD contrast, BOLDMT has higher insensitivity to B (0) inhomogeneities. BOLDMT may potentially serve as a reliable and novel biomarker for tumor oxygen extraction.

The main goal of this study was to use multimodality imaging methods to reveal the heterogeneity in prostate cancer and seek the correlation between the characteristic heterogeneity and tumor aggressiveness. Here we report the preliminary data on chemical exchange saturation transfer (CEST) and magnetization transfer (MT) magnetic resonance imaging (MRI) and redox scanning [cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imaging] of two aggressive human prostate tumor lines (DU-145 and PC-3) xenografted in athymic nude mice. The results obtained by these methods appeared to be consistent, with all showing a higher level of heterogeneity in DU-145 tumors than in PC-3 tumors. DU-145 tumors showed CEST maps with both positive and negative areas while PC-3 CEST maps were relatively homogeneous. The mean CEST value for PC-3, 23.0 ± 2.1 %, is at a significantly higher level (p < 0.05) than DU-145 (1.9 ± 6.7 %) at the peak of the CEST asymmetric curve (+2 ppm). Fp redox ratio (Fp/(NADH + Fp)) images exhibited localized highly oxidized regions in DU-145 tumors, whereas PC-3 tumors appeared to be less heterogeneous. These results suggest a possible role of metabolism in tumor progression. More studies, including an indolent prostate tumor line and with larger sample size, will be performed in the future to identify the biomarkers for prostate tumor aggressiveness.