Arterial Spin Labeling Perfusion of the Brain: Emerging Clinical Applications

Arterial spin labeling (ASL) is a magnetic resonance (MR) imaging technique used to assess cerebral blood flow noninvasively by magnetically labeling inflowing blood. In this article, the main labeling techniques, notably pulsed and pseudocontinuous ASL, as well as emerging clinical applications will be reviewed. In dementia, the pattern of hypoperfusion on ASL images closely matches the established patterns of hypometabolism on fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET) images due to the close coupling of perfusion and metabolism in the brain. This suggests that ASL might be considered as an alternative for FDG, reserving PET to be used for the molecular disease-specific amyloid and tau tracers. In stroke, ASL can be used to assess perfusion alterations both in the acute and the chronic phase. In arteriovenous malformations and dural arteriovenous fistulas, ASL is very sensitive to detect even small degrees of shunting. In epilepsy, ASL can be used to assess the epileptogenic focus, both in peri- and interictal period. In neoplasms, ASL is of particular interest in cases in which gadolinium-based perfusion is contraindicated (eg, allergy, renal impairment) and holds promise in differentiating tumor progression from benign causes of enhancement. Finally, various neurologic and psychiatric diseases including mild traumatic brain injury or posttraumatic stress disorder display alterations on ASL images in the absence of visualized structural changes. In the final part, current limitations and future developments of ASL techniques to improve clinical applicability, such as multiple inversion time ASL sequences to assess alterations of transit time, reproducibility and quantification of cerebral blood flow, and to measure cerebrovascular reserve, will be reviewed

Positron emissiontomography imaging of neuroinflammation in Multiple Sclerosis with a second generation translocator protein PET radioligand

This thesis describes a new approach for molecular imaging of neuroinflammation in Multiple Sclerosis (MS). My aim was to use the 2nd generation TSPO radioligand 18F-PBR111 to explore the potential of Positron Emission Tomography (PET) targeting the 18-kDa Translocator Protein (TSPO), as an in vivo biomarker of activated microglia in MS patients. This thesis addresses three research objectives. First, I characterised 18F-PBR111 PET signal in healthy controls’ brains and tested how it is affected by the TSPO gene polymorphism at rs6971. Second, I measured 18F-PBR111 uptake across white matter volumes segmented using structural MRI measures related to MS neuropathology. Third, I explored how 18F-PBR111 uptake in the hippocampus correlated with depressive symptoms and to the brain functional connectivity of the hippocampus. Eleven patients with relapsing-remitting MS and 22 age-matched healthy controls underwent 18F-PBR111 PET and MRI scans. Structural and functional MRI sequences were used to define conventional MS neuropathological markers and for the assessment of functional connectivity, respectively. I discovered that white matter 18F-PBR111 PET signal in healthy volunteers varied with TSPO genotype and correlated positively with age. In patients with MS, signal intensity in MRI-defined lesions was higher than that in normal-appearing white matter and correlated with the historical rate of progression of their disability. Hippocampal 18F-PBR111 uptake was higher in the MS patient group than in healthy volunteers and correlated with both depressive symptoms and functional connectivity of the hippocampus with frontal, temporal and parietal cortex. I thus discovered that this 2nd generation TSPO PET radiotracer, used in humans for the first time in our study, is sensitive to MS neuropathology consistent with recognized patterns of microglial activation and that differences between subjects can be related to disability progression. I also have discovered a novel relationship between this measure of hippocampal microglial activation and affective symptoms of MS.Open Acces

Perspectives on Nuclear Medicine for Molecular Diagnosis and Integrated Therapy

nuclear medicine; diagnostic radiolog

12 Chapters on Nuclear Medicine

The development of nuclear medicine as a medical specialty has resulted in the large-scale application of its effective imaging methods in everyday practice as a primary method of diagnosis. The introduction of positron-emitting tracers (PET) has represented another fundamental leap forward in the ability of nuclear medicine to exert a profound impact on patient management, while the ability to produce radioisotopes of different elements initiated a variety of tracer studies in biology and medicine, facilitating enhanced interactions of nuclear medicine specialists and specialists in other disciplines. At present, nuclear medicine is an essential part of diagnosis of many diseases, particularly in cardiologic, nephrologic and oncologic applications and it is well-established in its therapeutic approaches, notably in the treatment of thyroid cancers. Data from official sources of different countries confirm that more than 10-15 percent of expenditures on clinical imaging studies are spent on nuclear medicine procedures

PET-imaging in depression and antidepressant therapies : focus on the serotonin system and the cerebral glucose metabolism

The main scope of the research summarised in this dissertation comprises the use of positron emission tomography to investigate the role of the serotonin transporter in depression and antidepressant therapies. Hereby, several studies were performed using the PET radiotracer [11C]DASB, which specifically targets the serotonin transporter. To allow qualitative and safe research with this radiotracer, the first research topic focussed on the optimization of the radiotracer’s purification procedure and its quality control. Using this radiotracer, a first-in-dog study was carried out to investigate the radiotracer’s distribution and to define the appropriate image quantification methods. Subsequently, this radiotracer was used to perform a dose-occupancy in the dog to estimate the optimal dosing regimen to treat dogs with behavioural disorders with escitalopram. A second part of the dissertation focuses on rats and the current position of repetitive transcranial magnetic stimulation (rTMS) in the rat. Hereby, several additional objectives were put forward. The first objective comprised the evaluation of the accuracy of a for rodents adapted human neuronavigation system to perform rTMS in the rat. A second objective was the investigation of the construct validity of two depression models in terms of altered regional glucose metabolism. This was investigated via a PET study using the radiotracer [18F]FDG. Finally, for the preferred depression model, which was the one based on chronic corticosterone injections, the scope was extended from the serotonin transporter to the serotonin 5-HT1A and 5-HT2A receptors to explore the role of the serotonin system in the pathophysiology of this depression model in the rat. For this purpose, three radiotracers were applied: [11C]DASB, [18F]MPPF, and [18F]altanserin. This allowed to image the serotonin transporters, the 5-HT1A receptors, and the 5-HT2A receptors, respectively

Energy failure following traumatic brain injury: Potential mechanisms and impact of normobaric hyperoxia

Cerebral ischaemia is a frequent finding in post mortem studies following traumatic brain injury (TBI), but clinical studies using 15oxygen positron emission tomography (15O PET) suggest that classical ischaemia is uncommon beyond the first 24 hours after injury. Evidence of metabolic failure in the absence of classical ischaemia may represent ongoing neuronal dysfunction and progressive neuronal loss. Any therapeutic intervention that mitigates such metabolic derangements before they result in irreversible neuronal injury may improve tissue fate and improve the functional outcome for patients. Energy failure was spatially defined, characterised, and mapped using 15O and 18Fluoromisinidazole ([18F] FMISO) positron emission tomography. This enabled differentiation of classical ischaemia, diffusion hypoxia, and established infarction, and provided data on the dominant local mechanism at any given time after TBI. My thesis also aimed to examine the utility of diffusion tensor imaging and whole-brain proton MR spectroscopy (WB 1H MRS) as imaging biomarkers to investigate normobaric hyperoxia as a therapeutic option following traumatic brain injury (TBI). Using ([18F] FMISO PET evidence of tissue hypoxia consistent with microvascular ischaemia was found across the injured brain. The impact of normobaric hyperoxia (NBH) was examined in a clinical TBI cohort using diffusion tensor imaging and WB 1H MRS. Some evidence of benefit was found within the perilesional brain, but further studies should examine the value of a longer period of exposure to NBH and whether this has implications for functional outcome.AAGBI, MRC, Wellcome trus

CT Scanning

Since its introduction in 1972, X-ray computed tomography (CT) has evolved into an essential diagnostic imaging tool for a continually increasing variety of clinical applications. The goal of this book was not simply to summarize currently available CT imaging techniques but also to provide clinical perspectives, advances in hybrid technologies, new applications other than medicine and an outlook on future developments. Major experts in this growing field contributed to this book, which is geared to radiologists, orthopedic surgeons, engineers, and clinical and basic researchers. We believe that CT scanning is an effective and essential tools in treatment planning, basic understanding of physiology, and and tackling the ever-increasing challenge of diagnosis in our society

The functional and structural associations of aberrant microglial activity in major depressive disorder

Background: Major depressive disorder (MDD) is a debilitating mental illness that has been linked to increases in markers of inflammation, as well as to changes in brain functional and structural connectivity, particularly between the insula and the subgenual anterior cingulate cortex (sgACC). In this study, we directly related inflammation and dysconnectivity in treatment-resistant MDD by concurrently measuring the following: microglial activity with [18F]N-2-(fluoroethoxyl)benzyl-N-(4phenoxypyridin-3-yl)acetamide ([18F]FEPPA) positron emission tomography (PET); the severity of MDD; and functional or structural connectivity among insula or sgACC nodes. Methods: Twelve patients with treatment-resistant MDD (8 female, 4 male; mean age ± standard deviation 54.9 ± 4.5 years and 23 healthy controls (11 female, 12 male; 60.3 ± 8.5 years) completed a hybrid [18F]FEPPA PET and MRI acquisition. From these, we extracted relative standardized uptake values for [18F]FEPPA activity and Pearson r-to-z scores representing functional connectivity from our regions of interest. We extracted diffusion tensor imaging metrics from the cingulum bundle, a key white matter bundle in MDD. We performed regressions to relate microglial activity with functional connectivity, structural connectivity and scores on the 17-item Hamilton Depression Rating Scale. Results: We found significantly increased [18F]FEPPA uptake in the left sgACC in patients with treatment-resistant MDD compared to healthy controls. Patients with MDD also had a reduction in connectivity between the sgACC and the insula. The [18F]FEPPA uptake in the left sgACC was significantly related to functional connectivity with the insula, and to the structural connectivity of the cingulum bundle. [18F]FEPPA uptake also predicted scores on the Hamilton Depression Rating Scale. Limitations: A relatively small sample size, lack of functional task data and concomitant medication use may have affected our findings. Conclusion: We present preliminary evidence linking a network-level dysfunction relevant to the pathophysiology of depression and related to increased microglial activity in MDD

Functional brain imaging in the dog : Single Photon Emission Tomography as a research and clinical tool for the investigation of canine brain physiology and pathophysiology

summary of doctoral dissertatio