Central Nervous System Function in Youth With Type 1 Diabetes 12 Years After Disease Onset

OBJECTIVE—In this study, we used neurocognitive assessment and neuroimaging to examine brain function in youth with type 1 diabetes studied prospectively from diagnosis

Perfusion and diffusion magnetic resonance imaging studies of cerebral ischaemia

Magnetic resonance imaging (MRI) has opened up new avenues of anatomical and physiological research. Its non-invasive nature and the ability to obtain images with a high degree of spatial resolution, have been exploited in this research as well as in routine clinical investigations. However, the use of standard MRI techniques in the investigation of the acute phases of cerebrovascular diseases such as stroke, has been hampered by impaired sensitivity to detect areas of ischaemic damage. The relatively recent development of the MRI techniques of diffusion and perfusion imaging, described in this thesis, have the capability to fill this gap. The diffusive mobility of water is a sensitive indicator of tissue energy status, and perfusion imaging provides quantitative measurements of cerebral blood flow (CBF). This thesis describes the implementation of these two techniques in experimental studies of cerebral ischaemia. Special emphasis is placed upon the improvement of the temporal resolution of these methods in order that time course studies of the rapidly evolving pathophysiology can be carried out. In particular, an innovative modification of the spin-labelling perfusion technique of flow-sensitive alternating inversion recovery (FAIR), has been developed that allows rapid, mapping of CBF. This method was implemented in an important study of reperfusion injury. High time-resolution sequences for rapid, quantitative diffusion imaging were implemented on both high-field and low-field MRI systems. The high-field environment sensitises the images to various artefacts and a novel enhancement of a standard rapid imaging technique was required in order to obtain accurate measurements. On the low-field system, fast imaging of the trace of the diffusion tensor (trace(D)) was optimised and employed during a study of repeated ischaemic episodes that is a model of transient ischaemic attacks. The combination of these two MRI techniques has provided unique insights into experimental cerebral ischaemia

Efficacy of Deep TMS with the H1 Coil for Anxious Depression

(1) Background: While the therapeutic efficacy of Transcranial Magnetic Stimulation (TMS) for major depressive disorder (MDD) is well established, less is known about the technique’s efficacy for treating comorbid anxiety. (2) Methods: Data were retrospectively analyzed from randomized controlled trials (RCTs) that used Deep TMS with the H1 Coil for MDD treatment. The primary endpoint was the difference relative to sham treatment following 4 weeks of stimulation. The effect size was compared to literature values for superficial TMS and medication treatments. (3) Results: In the pivotal RCT, active Deep TMS compared with sham treatment showed significantly larger improvements in anxiety score (effect size = 0.34, p = 0.03 (FDR)) which were sustained until 16 weeks (effect size = 0.35, p = 0.04). The pooled effect size between all the RCTs was 0.55, which compares favorably to alternative treatments. A direct comparison to Figure-8 Coil treatment indicated that treatment with the H1 Coil was significantly more effective (p = 0.042). In contrast to previously reported studies using superficial TMS and medication for which anxiety has been shown to be a negative predictor of effectiveness, higher baseline anxiety was found to be predictive of successful outcome for the H1-Coil treatment. (4) Conclusions: Deep TMS is effective in treating comorbid anxiety in MDD and, unlike alternative treatments, the outcome does not appear to be adversely affected by high baseline anxiety levels

Quantitative imaging assessment of blood-brain barrier permeability in humans

Abstract The blood–brain barrier (BBB) is a functional and structural barrier separating the intravascular and neuropil compartments of the brain. It characterizes the vascular bed and is essential for normal brain functions. Dysfunction in the BBB properties have been described in most common neurological disorders, such as stroke, traumatic injuries, intracerebral hemorrhage, tumors, epilepsy and neurodegenerative disorders. It is now obvious that the BBB plays an important role in normal brain activity, stressing the need for applicable imaging and assessment methods. Recent advancements in imaging techniques now make it possible to establish sensitive and quantitative methods for the assessment of BBB permeability. However, most of the existing techniques require complicated and demanding dynamic scanning protocols that are impractical and cannot be fulfilled in some cases. We review existing methods for the evaluation of BBB permeability, focusing on quantitative magnetic resonance-based approaches and discuss their drawbacks and limitations. In light of those limitations we propose two new approaches for BBB assessment with less demanding imaging sequences: the “post-pre” and the “linear dynamic” methods, both allow semi-quantitative permeability assessment and localization of dysfunctional BBB with simple/partial dynamic imaging protocols and easy-to-apply analysis algorithms. We present preliminary results and show an example which compares these new methods with the existing standard assessment method. We strongly believe that the establishment of such “easy to use” and reliable imaging methods is essential before BBB assessment can become a routine clinical tool. Large clinical trials are awaited to fully understand the significance of BBB permeability as a biomarker and target for treatment in neurological disorders.</p

The Right Supramarginal Gyrus Is Important for Proprioception in Healthy and Stroke-Affected Participants: A Functional MRI Study

Human proprioception is essential for motor control, yet its central processing is still debated. Previous studies of passive movements and illusory vibration have reported inconsistent activation patterns related to proprioception, particularly in high-order sensorimotor cortices. We investigated brain activation specific to proprioception, its laterality, and changes following stroke. Twelve healthy and three stroke-affected individuals with proprioceptive deficits participated. Proprioception was assessed clinically with the Wrist Position Sense Test, and participants underwent functional magnetic resonance imaging scanning. An event-related study design was used, where each proprioceptive stimulus of passive wrist movement was followed by a motor response of mirror -copying with the other wrist. Left (LWP) and right (RWP) wrist proprioception were tested separately. Laterality indices (LIs) were calculated for the main cortical regions activated during proprioception. We found proprioception-related brain activation in high-order sensorimotor cortices in healthy participants especially in the supramarginal gyrus (SMG LWP z = 4.51, RWP z = 4.24) and the dorsal premotor cortex (PMd LWP z = 4.10, RWP z = 3.93). Right hemispheric dominance was observed in the SMG (LI LWP mean 0.41, SD 0.22; RWP 0.29, SD 0.20), and to a lesser degree in the PMd (LI LWP 0.34, SD 0.17; RWP 0.13, SD 0.25). In stroke-affected participants, the main difference in proprioception-related brain activation was reduced laterality in the right SMG. Our findings indicate that the SMG and PMd play a key role in proprioception probably due to their role in spatial processing and motor control, respectively. The findings from stroke--affected individuals suggest that decreased right SMG function may be associated with decreased proprioception. We recommend that clinicians pay particular attention to the assessment and rehabilitation of proprioception following right hemispheric lesions

A technique for the measurement of renal ATP in a large animal model of septic shock

BACKGROUND: The mechanisms responsible for acute renal failure in sepsis are not understood. Measurement of tissue ATP might help to understand this process but, in the large animal, it is hampered by major technical difficulties. OBJECTIVE: To develop a technique to monitor ATP in the kidney of a large mammal during the induction of septic shock and then circulatory arrest. METHODS: Implantation of a custom-made phosphorus coil around the left kidney. Induction of septic shock by intravenous E. coli administration. Acquisition of 31 P magnetic resonance (MR) spectroscopic data at 3-tesla before and during septic shock over several hours. Induction of euthanasia and measurement of the same 31 P signal immediately and thirty minutes after circulatory arrest. RESULTS: Clear reproducible 31 P MR spectra were obtained before and after the induction of septic shock and euthanasia. They indicated limited changes in ATP during septic shock. An expected rapid and dramatic decrease in ATP occurred with euthanasia. CONCLUSIONS: It is possible to sequentially monitor renal bioenergetics in a large mammal during septic shock using an implanted custom-made phosphorus coil and 3-tesla MR technology. This technique offers a novel approach to the investigation of septic renal failure

Technique for the simultaneous measurement of renal ATP, blood flow and pH in a large animal model of septic shock

BACKGROUND: Simultaneous measurement of renal blood flow, renal ATP, renal pH and mean arterial pressure (MAP) might help investigators understand the mechanisms responsible for acute renal failure (ARF) in sepsis. OBJECTIVES: (1) To develop a technique to simultaneously measure MAP, renal blood flow, renal ATP and renal pH in a large mammal during severe sepsis and after circulatory arrest; and (2) To describe preliminary observations during such measurements. METHODS: We implanted a custom-made phosphorus coil around the left kidney and a magnetic resonance-compatible blood flow probe around the renal artery of an adult Merino ewe. We induced severe sepsis by intravenous administration of Escherichia coli and obtained 31P magnetic resonance spectroscopic data at 3tesla, and continuous blood flow and MAP data before and during severe sepsis over several hours. We induced circulatory arrest with potassium chloride and measured the same 31P signal immediately and again 30 minutes later. RESULTS: We successfully and simultaneously measured MAP, renal blood flow, renal ATP and renal pH in a large mammal during severe sepsis and induced circulatory arrest. With these techniques, we observed that, despite marked hypotension, there were limited changes in renal ATP and renal pH, and that renal blood flow increased. A rapid and dramatic decrease in ATP and pH occurred with circulatory arrest. CONCLUSIONS: We have developed a technique to simultaneously monitor MAP, renal blood flow, ATP and pH in a large mammal during severe sepsis. Our initial observations indicate preservation of renal ATP in septic shock