In vivo 3D brain and extremity MRI at 50 mT using a permanent magnet Halbach array.

PURPOSE: To design a low-cost, portable permanent magnet-based MRI system capable of obtaining in vivo MR images within a reasonable scan time. METHODS: A discretized Halbach permanent magnet array with a clear bore diameter of 27 cm was designed for operation at 50 mT. Custom-built gradient coils, RF coil, gradient amplifiers, and RF amplifier were integrated and tested on both phantoms and in vivo. RESULTS: Phantom results showed that the gradient nonlinearity in the y-direction and z-direction was less than 5% over a 15-cm FOV and did not need correcting. For the x-direction, it was significantly greater, but could be partially corrected in postprocessing. Three-dimensional in vivo scans of the brain of a healthy volunteer using a turbo spin-echo sequence were acquired at a spatial resolution of 4 × 4 × 4 mm in a time of about 2 minutes. The T1 -weighted and T2 -weighted scans showed a good degree of tissue contrast. In addition, in vivo scans of the knee of a healthy volunteer were acquired at a spatial resolution of about 3 × 2 × 2 mm within 12 minutes to show the applicability of the system to extremity imaging. CONCLUSION: This work has shown that it is possible to construct a low-field MRI unit with hardware components costing less than 10 000 Euros, which is able to acquire human images in vivo within a reasonable data-acquisition time. The system has a high degree of portability with magnet weight of approximately 75 kg, gradient and RF amplifiers each 15 kg, gradient coils 10 kg, and spectrometer 5 kg.

High temporal resolution arterial spin labeling MRI with whole-brain coverage by combining time-encoding with Look-Locker and simultaneous multi-slice imaging.

PURPOSE: The goal of this study was to achieve high temporal resolution, multi-time point pseudo-continuous arterial spin labeling (pCASL) MRI in a time-efficient manner, while maintaining whole-brain coverage. METHODS: A Hadamard 8-matrix was used to dynamically encode the pCASL labeling train, thereby providing the first source of temporal information. The second method for obtaining dynamic arterial spin labeling (ASL) signal consisted of a Look-Locker (LL) readout of 4 phases that are acquired with a flip-angle sweep to maintain constant sensitivity over the phases. To obtain whole-brain coverage in the short LL interval, 4 slices were excited simultaneously by multi-banded radiofrequency pulses. After subtraction according to the Hadamard scheme, the ASL signal was corrected for the use of the flip-angle sweep and background suppression pulses. The BASIL toolkit of the Oxford Centre for FMRIB was used to quantify the ASL signal. RESULTS: By combining a time-encoded pCASL labeling scheme with an LL readout and simultaneous multi-slice acquisition, 28 time points of 16 slices with a 75- or 150-ms time resolution were acquired in a total scan time of 10 minutes 20 seconds, from which cerebral blood flow (CBF) maps, arterial transit time maps, and arterial blood volume could be determined. CONCLUSION: Whole-brain ASL images were acquired with a 75-ms time resolution for the angiography and 150-ms resolution for the perfusion phase by combining the proposed techniques. Reducing the total scan time to 1 minute 18 seconds still resulted in reasonable CBF maps, which demonstrates the feasibility of this approach for practical studies on brain hemodynamics.

Comparison of perfusion signal acquired by arterial spin labeling-prepared intravoxel incoherent motion (IVIM) MRI and conventional IVIM MRI to unravel the origin of the IVIM signal.

PURPOSE: Applications of intravoxel incoherent motion (IVIM) imaging in the brain are scarce, whereas it has been successfully applied in other organs with promising results. To better understand the cerebral IVIM signal, the diffusion properties of the arterial blood flow within different parts of the cerebral vascular tree (i.e., different generations of the branching pattern) were isolated and measured by employing an arterial spin labeling (ASL) preparation module before an IVIM readout. METHODS: ASL preparation was achieved by T1 -adjusted time-encoded pseudo-continuous ASL (te-pCASL). The IVIM readout module was achieved by introducing bipolar gradients immediately after the excitation pulse. The results of ASL-IVIM were compared with those of conventional IVIM to improve our understanding of the signal generation process of IVIM. RESULTS: The pseudo-diffusion coefficient D* as calculated from ASL-IVIM data was found to decrease exponentially for postlabeling delays (PLDs) between 883 ms and 2176 ms, becoming relatively stable for PLDs longer than 2176 ms. The fast compartment of the conventional IVIM-experiment shows comparable apparent diffusion values to the ASL signal with PLDs between 1747 ms and 2176 ms. At the longest PLDs, the observed D* values (4.0 ± 2.8 × 10-3 mm2 /s) are approximately 4.5 times higher than the slow compartment (0.90 ± 0.05 × 10-3 mm2 /s) of the conventional IVIM experiment. CONCLUSION: This study showed much more complicated diffusion properties of vascular signal than the conventionally assumed single D* of the perfusion compartment in the two-compartment model of IVIM (biexponential behavior). Magn Reson Med 79:723-729, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous measurement of brain perfusion and labeling efficiency in a single pseudo-continuous arterial spin labeling scan.

PURPOSE: The aim of this study was to propose, optimize, and validate a pseudo-continuous arterial spin labeling (pCASL) sequence for simultaneous measurement of brain perfusion and labeling efficiency. METHODS: The proposed sequence incorporates the labeling efficiency measurement into the postlabeling delay period of a conventional perfusion pCASL sequence by using the time-encoding approach. In vivo validation experiments were performed on nine young subjects by comparing it to separate perfusion and labeling efficiency sequences. Sensitivity of the proposed combined sequence for measuring labeling efficiency changes was further addressed by varying the flip angles of the pCASL labeling radiofrequency pulses. RESULTS: The proposed combined sequence decreased the perfusion signal by ∼4% and a lower labeling efficiency (by ∼10%) was found as compared to the separate sequences. However, the temporal signal-noise-ratio of the perfusion signal remained unchanged. When the pCASL flip angle was decreased to a suboptimal setting, a strong correlation was found between the combined and the separate sequences for the relative change in pCASL perfusion signal as well as for the relative change in labeling efficiency. High correlation was also observed between relative changes in perfusion signal and the measured labeling efficiencies. CONCLUSION: The proposed sequence allows simultaneous measurement of brain perfusion and labeling efficiency with high time-efficiency at the price of only a small compromise in measurement accuracy. The additional labeling efficiency measurement can be used to facilitate qualitative interpretation of pCASL perfusion images. Magn Reson Med 79:1922-1930, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Transit time mapping in the mouse brain using time-encoded pCASL.

The cerebral blood flow (CBF) is a potential biomarker for neurological disease. However, the arterial transit time (ATT) of the labeled blood is known to potentially affect CBF quantification. Furthermore, ATT could be an interesting biomarker in itself, as it may reflect underlying macro- and microvascular pathologies. Currently, no optimized magnetic resonance imaging (MRI) sequence exists to measure ATT in mice. Recently, time-encoded labeling schemes have been implemented in rats and humans, enabling ATT mapping with higher signal-to-noise ratio (SNR) and shorter scan time than multi-delay arterial spin labeling (ASL). In this study, we show that time-encoded pseudo-continuous arterial spin labeling (te-pCASL) also enables transit time measurements in mice. As an optimal design that takes the fast blood flow in mice into account, time encoding with 11 sub-boli of 50 ms is proposed to accurately probe the inflow of labeled blood. For perfusion imaging, a separate, traditional pCASL scan was employed. From the six studied brain regions, the hippocampus showed the shortest ATT (169 ± 11 ms) and the auditory/visual cortex showed the longest (284 ± 16 ms). Furthermore, ATT was found to be preserved in old wild-type mice. In a mouse with an induced carotid artery occlusion, prolongation of ATT was shown. In conclusion, this study shows the successful implementation of te-pCASL in mice, making it possible, for the first time, to measure ATT in mice in a time-efficient manner.

Clinical evaluation of ultra-high-field MRI for three-dimensional visualisation of tumour size in uveal melanoma patients, with direct relevance to treatment planning.

OBJECTIVES: To assess the tumour dimensions in uveal melanoma patients using 7-T ocular MRI and compare these values with conventional ultrasound imaging to provide improved information for treatment options. MATERIALS AND METHODS: Ten uveal melanoma patients were examined on a 7-T MRI system using a custom-built eye coil and dedicated 3D scan sequences to minimise eye-motion-induced image artefacts. The maximum tumour prominence was estimated from the three-dimensional images and compared with the standard clinical evaluation from 2D ultrasound images. RESULTS: The MRI protocols resulted in high-resolution motion-free images of the eye in which the tumour and surrounding tissues could clearly be discriminated. For eight of the ten patients the MR images showed a slightly different value of tumour prominence (average 1.0 mm difference) compared to the ultrasound measurements, which can be attributed to the oblique cuts through the tumour made by the ultrasound. For two of these patients the more accurate results from the MR images changed the treatment plan, with the smaller tumour dimensions making them eligible for eye-preserving therapy. CONCLUSION: High-field ocular MRI can yield a more accurate measurement of the tumour dimensions than conventional ultrasound, which can result in significant changes in the prescribed treatment.

Time-efficient determination of spin compartments by time-encoded pCASL T2-relaxation-under-spin-tagging and its application in hemodynamic characterization of the cerebral border zones.

Information on water-transport across the blood-brain barrier can be determined from the T2 of the arterial spin labeling (ASL) signal. However, the current approach of using separate acquisitions of multiple inversion times is too time-consuming for clinical (research) applications. The aim of this study was to improve the time-efficiency of this method by combining it with time-encoded pseudo-continuous ASL (te-pCASL). Furthermore, the hemodynamic properties of the border zone regions in the brains of healthy, young volunteers were characterized as an example application. The use of te-pCASL instead of multi-TI pCASL significantly reduced the total scan duration, while providing a higher temporal resolution. A significantly lower cerebral blood flow (CBF) was found in the border zone regions compared with the central regions in both the posterior and the middle cerebral artery (MCA) flow territory. The arterial transit time (ATT) was almost two times longer in the border zone regions than in the central regions (p<0.05), with an average delay in ATT of 382ms in the posterior and 539ms in the MCA flow territory. When corrected for the ATT, the change in T2 over time was not significantly different for the border zones as compared to the central regions. In conclusion, te-pCASL-TRUST provided a time-efficient method to distinguish spin compartments based on their T2. The ATT in the border zone is significantly longer than in the central region. However, the exchange of the label from the arterial to the tissue compartment appears to be at a similar rate.

Effects of background suppression on the sensitivity of dual-echo arterial spin labeling MRI for BOLD and CBF signal changes.

Dual-echo arterial spin labeling (DE-ASL) enables the simultaneous acquisition of BOLD and CBF fMRI data and is often used for calibrated BOLD and cerebrovascular CO2 reactivity measurements. DE-ASL, like all ASL techniques, suffers from a low intrinsic CBF SNR, which can be improved by suppressing the background signal via the inclusion of additional inversion pulses. However, until now this approach has been considered to be undesirable for DE-ASL, because the BOLD signal is extracted from the background signal and attenuating the background signal could decrease the sensitivity of DE-ASL scans for BOLD changes. In this study, the effect of background suppression on the sensitivity of DE-ASL MRI for BOLD and CBF signal changes with a visual stimulation paradigm was studied. Results showed that with an average background suppression level of 70% the BOLD sensitivity of DE-ASL MRI decreases slightly (15%), while the CBF sensitivity of the scans increased by almost a factor-of-two (81%). These findings support the conclusion that the gains in CBF sensitivity of DE-ASL MRI due to background suppression outweigh the slight decrease in sensitivity of these scans for BOLD changes, and thus that background suppression is highly recommended for DE-ASL.

Acceleration-selective arterial spin labeling.

In this study, a new arterial spin labeling (ASL) method with spatially nonselective labeling is introduced, based on the acceleration of flowing spins, which is able to image brain perfusion with minimal contamination from venous signal. This method is termed acceleration-selective ASL (AccASL) and resembles velocity-selective ASL (VSASL), with the difference that AccASL is able to discriminate between arterial and venous components in a single preparation module due to the higher acceleration on the arterial side of the microvasculature, whereas VSASL cannot make this distinction unless a second labeling module is used. A difference between AccASL and VSASL is that AccASL is mainly cerebral blood volume weighted, whereas VSASL is cerebral blood flow weighted. AccASL exploits the principles of acceleration-encoded magnetic resonance angiography by using motion-sensitizing gradients in a T2 -preparation module. This method is demonstrated in healthy volunteers for a range of cutoff accelerations. Additionally, AccASL is compared with VSASL and pseudo-continuous ASL, and its feasibility in functional MRI is demonstrated. Compared with VSASL with a single labeling module, a strong and significant reduction in venous label is observed. The resulting signal-to-noise ratio is comparable to pseudo-continuous ASL and robust activation of the visual cortex is observed.

Time-encoded pseudocontinuous arterial spin labeling: basic properties and timing strategies for human applications.

PURPOSE: In this study, the basic properties and requirements of time-encoded pseudocontinuous arterial spin labeling (te-pCASL) are investigated. Also, the extra degree of freedom delivered by changing block durations is explored. METHODS: First, the minimal duration of encoding blocks, the influence of cardiac triggering, and the effect of dividing the labeling period into blocks are evaluated. Two new strategies for timing the encoding blocks in te-pCASL are introduced: variable block duration to compensate for T1-decay and the free lunch approach that uses the postlabeling delay time that is idle in standard pCASL to acquire arterial transit time (ATT) information. Simulations are used to probe possible signal losses. RESULTS: No signal loss was found when dividing the labeling period into blocks with duration >50 ms. In time-encoded perfusion imaging, no cardiac triggering is required. Summation of results for individual blocks in te-pCASL postprocessing causes severe loss of temporal SNR. Quality of cerebral blood flow (CBF) maps was not affected by the encoding line order. CONCLUSION: Adjusting the timing of encoding blocks in te-pCASL allows for tailoring the acquisition to specific applications. With the free lunch setup, te-pCASL delivers CBF and high resolution ATT maps within a single scan, with a small penalty in tSNR.

Subject tolerance of 7 T MRI examinations.

PURPOSE: To determine the subjective experiences and the sources of discomfort for subjects undergoing 7 T magnetic resonance imaging (MRI) examinations on a whole-body 7 T system in a hospital setting MATERIALS AND METHODS: A postscan survey was filled out by 101 healthy subjects who participated in a 7 T examination. All participants answered questions regarding different potential sensations of discomfort including dizziness, claustrophobia, and scanner noise. RESULTS: Dizziness was reported most frequently, with 34% of subjects experiencing dizziness while moving into the scanner and 30% while moving out of the magnet. Scanner noise was also frequently mentioned as uncomfortable (33% of the subjects). In 11% of the cases a metallic taste was reported. The overall experience was rated by 3% as unpleasant, 51% as neutral, and 46% as pleasant. CONCLUSION: The reported side effects are larger than previously reported for lower field strengths. However, overall, 7 T examinations are well tolerated, with only 3% of subjects rating it as unpleasant. These results agree well with previous in-depth studies, and provide further evidence that 7 T MRI would be accepted by patients in clinical practice.

Quantitative assessment of the effects of high-permittivity pads in 7 Tesla MRI of the brain.

The use of high-permittivity materials has been shown to be an effective method for increasing transmit and receive sensitivity in areas of low-signal intensity in the brain at high field. Results in this article show that the use of these materials does not increase the intercoil coupling for a phased array receive coil, does not have any detrimental effects on the B(0) homogeneity within the brain, and does not affect the specific absorption rate distribution within the head. Areas of the brain close to the pads exhibit significant increases (>100%) in transmit field efficiency, but areas further away show a less pronounced (~10%) decrease due to the homogenization of the transmit field and the loss introduced by the dielectric pads.

Food cues do not modulate the neuroendocrine response to a prolonged fast in healthy men.

INTRODUCTION: Dietary restriction benefits health and increases lifespan in several species. Food odorants restrain the beneficial effects of dietary restriction in Drosophila melanogaster. We hypothesized that the presence of visual and odorous food stimuli during a prolonged fast modifies the neuroendocrine and metabolic response to fasting in humans. SUBJECTS AND METHODS: In this randomized, crossover intervention study, healthy young men (n = 12) fasted twice for 60 h; once in the presence and once in the absence of food-related visual and odorous stimuli. At baseline and on the last morning of each intervention, an oral glucose tolerance test (OGTT) was performed. During the OGTT, blood was sampled and a functional MRI scan was made. RESULTS: The main effects of prolonged fasting were: (1) decreased plasma thyroid stimulating hormone and triiodothyronine levels; (2) downregulation of the pituitary-gonadal axis; (3) reduced plasma glucose and insulin concentrations, but increased glucose and insulin responses to glucose ingestion; (4) altered hypothalamic blood oxygenation level-dependent (BOLD) signal in response to the glucose load (particularly during the first 20 min after ingestion); (5) increased resting energy expenditure. Exposure to food cues did not affect these parameters. CONCLUSION: This study shows that 60 h of fasting in young men (1) decreases the hypothalamic BOLD signal in response to glucose ingestion; (2) induces glucose intolerance; (3) increases resting energy expenditure, and (4) downregulates the pituitary-thyroid and pituitary-gonadal axes. Exposure to visual and odorous food cues did not alter these metabolic and neuroendocrine adaptations to nutrient deprivation.

Functional and structural diversification of the Anguimorpha lizard venom system.

Venom has only been recently discovered to be a basal trait of the Anguimorpha lizards. Consequently, very little is known about the timings of toxin recruitment events, venom protein molecular evolution, or even the relative physical diversifications of the venom system itself. A multidisciplinary approach was used to examine the evolution across the full taxonomical range of this ∼130 million-year-old clade. Analysis of cDNA libraries revealed complex venom transcriptomes. Most notably, three new cardioactive peptide toxin types were discovered (celestoxin, cholecystokinin, and YY peptides). The latter two represent additional examples of convergent use of genes in toxic arsenals, both having previously been documented as components of frog skin defensive chemical secretions. Two other novel venom gland-overexpressed modified versions of other protein frameworks were also recovered from the libraries (epididymal secretory protein and ribonuclease). Lectin, hyaluronidase, and veficolin toxin types were sequenced for the first time from lizard venoms and shown to be homologous to the snake venom forms. In contrast, phylogenetic analyses demonstrated that the lizard natriuretic peptide toxins were recruited independently of the form in snake venoms. The de novo evolution of helokinestatin peptide toxin encoding domains within the lizard venom natriuretic gene was revealed to be exclusive to the helodermatid/anguid subclade. New isoforms were sequenced for cysteine-rich secretory protein, kallikrein, and phospholipase A(2) toxins. Venom gland morphological analysis revealed extensive evolutionary tinkering. Anguid glands are characterized by thin capsules and mixed glands, serous at the bottom of the lobule and mucous toward the apex. Twice, independently this arrangement was segregated into specialized serous protein-secreting glands with thick capsules with the mucous lobules now distinct (Heloderma and the Lanthanotus/Varanus clade). The results obtained highlight the importance of utilizing evolution-based search strategies for biodiscovery and emphasize the largely untapped drug design and development potential of lizard venoms.

Feasibility of pseudocontinuous arterial spin labeling at 7 T with whole-brain coverage.

OBJECT: We studied the feasibility of pseudocontinuous arterial spin labeling (pCASL) at 7 T. MATERIALS AND METHODS: Simulations were performed to find the optimal labeling parameters for pCASL, with particular attention to the maximum-allowed specific absorption rate (SAR). Subsequently, pCASL experiments (four volunteers) were performed to find the B1 efficiency at the labeling position with and without high-permittivity pads placed around the head, and to study the optimal labeling duration (four separate volunteers). Finally, feasibility of whole-brain pCASL imaging was tested. RESULTS: Simulations showed that a lower B1 efficiency should be compensated by a lower effective flip angle of the labeling, a moderately shorter labeling duration, and a longer repetition time. B1 efficiency in the internal carotid arteries just below the carotid siphon was approximately 55% and 35% with and without high-permittivity pads, respectively. In vivo experiments showed an optimal labeling duration of 1,500 ms, although longer labeling durations up to 2,500 ms resulted in similar signal-to-noise efficiency. Whole-brain pCASL imaging was demonstrated in a single volunteer. CONCLUSION: Despite decreased B1 efficiency, sufficient labeling efficiency can be achieved for whole-brain pCASL at 7 T with high-permittivity pads. However, image quality is still limited compared with 3 T, probably due to imaging instabilities, and further research is needed to elucidate this.

Can arterial spin labeling detect white matter perfusion signal?

Since the invention of arterial spin labeling (ASL) it has been acknowledged that ASL does not allow reliable detection of a white matter (WM) perfusion signal. However, recent developments such as pseudo-continuous labeling and background suppression have improved the quality. The goal of this research was to study the ability of these newer ASL sequences to detect WM perfusion signal. Background suppressed pseudo-continuous ASL was implemented at 3T with multislice 2D readout after 1525 ms. In five volunteers it was shown that 10 min scanning resulted in significant perfusion signal in 70% of WM voxels. Increasing the labeling and delay time did not lead to a higher percentage. In 27 normal volunteers it was found that 35 averages are necessary to detect significant WM signal, but 150 averages are needed to detect signal in the deep WM. Finally, it was shown in a patient with a cerebral arteriovenous malformation that pseudo-continuous ASL enabled the depiction of hypointense WM perfusion signal, although dynamic susceptibility contrast MRI showed that this region was merely showing delayed arrival of contrast agent than hypoperfusion. It can be concluded that, except within the deep WM, ASL is sensitive enough to detect WM perfusion signal and perfusion deficits.

Advances in arterial spin labelling MRI methods for measuring perfusion and collateral flow.

With the publication in 2015 of the consensus statement by the perfusion study group of the International Society for Magnetic Resonance in Medicine (ISMRM) and the EU-COST action 'ASL in dementia' on the implementation of arterial spin labelling MRI (ASL) in a clinical setting, the development of ASL can be considered to have become mature and ready for clinical prime-time. In this review article new developments and remaining issues will be discussed, especially focusing on quantification of ASL as well as on new technological developments of ASL for perfusion imaging and flow territory mapping. Uncertainty of the achieved labelling efficiency in pseudo-continuous ASL (pCASL) as well as the presence of arterial transit time artefacts, can be considered the main remaining challenges for the use of quantitative cerebral blood flow (CBF) values. New developments in ASL centre around time-efficient acquisition of dynamic ASL-images by means of time-encoded pCASL and diversification of information content, for example by combined 4D-angiography with perfusion imaging. Current vessel-encoded and super-selective pCASL-methodology have developed into easily applied flow-territory mapping methods providing relevant clinical information with highly similar information content as digital subtraction angiography (DSA), the current clinical standard. Both approaches seem therefore to be ready for clinical use.

Validation of a pharmacological model for mitochondrial dysfunction in healthy subjects using simvastatin: A randomized placebo-controlled proof-of-pharmacology study.

Proof-of-pharmacology models to study compounds in healthy subjects offer multiple advantages. Simvastatin is known to induce mitochondrial dysfunction at least partly by depletion of co-enzyme Q10. The goal of this study was to evaluate a model of simvastatin-induced mitochondrial dysfunction in healthy subjects and to determine whether mitochondrial dysfunction could be pharmacologically reversed by treatment with co-enzyme Q10 (ubiquinol). Subjects received simvastatin 40mg/day for 8 weeks. After 4 weeks, subjects were randomized to receive ubiquinol 300mg/day or placebo in a double-blinded fashion. Mitochondrial function was assessed by measuring the phosphocreatine recovery time (τ-PCr) using phosphorous Magnetic Resonance Spectroscopy (31P-MRS) after in-magnet exercise. After 4 weeks of simvastatin treatment, τ-PCr prolonged with 15.2% compared to baseline, (95%CI, 2.5-29.4%; P = 0.018, Fig. 3). After 8 weeks, τ-PCr further prolonged to 37.27s in the placebo group (prolongation of 18.5% compared to baseline, still significantly prolonged, 95%CI, 1.1-38.9%; P = 0.037), but shortened to 33.81s in the ubiquinol group (prolongation of 9.1% compared to baseline, no longer significantly prolonged, 95%CI, -7.9 to 29.2%; P = 0.31). At 8 weeks, there was no significant difference between groups (difference of 8.2%, 95%CI, -14.5 to 37.0%; P = 0.51). Simvastatin induces subclinical mitochondrial dysfunction in healthy subjects, which can be partly reversed by treatment with ubiquinol. This model of pharmacologically induced and reversed mitochondrial dysfunction can be used to study the effects of compounds that enhance mitochondrial function in healthy subjects.

Hypothalamic BOLD response to glucose intake and hypothalamic volume are similar in anorexia nervosa and healthy control subjects.

BACKGROUND: Inconsistent findings about the neurobiology of Anorexia Nervosa (AN) hinder the development of effective treatments for this severe mental disorder. Therefore, the need arises for elucidation of neurobiological factors involved in the pathophysiology of AN. The hypothalamus plays a key role in the neurobiological processes that govern food intake and energy homeostasis, processes that are disturbed in anorexia nervosa (AN). The present study will assess the hypothalamic response to energy intake and the hypothalamic structure in patients with AN and healthy controls. METHODS: Ten women aged 18-30 years diagnosed with AN and 11 healthy, lean (BMI < 23 kg/m(2)) women in the same age range were recruited. We used functional magnetic resonance imaging (MRI) to determine function of the hypothalamus in response to glucose. Structural MRI was used to determine differences in hypothalamic volume and local gray matter volume using manual segmentation and voxel-based morphometry. RESULTS: No differences were found in hypothalamic volume and neuronal activity in response to a glucose load between the patients and controls. Whole brain structural analysis showed a significant decrease in gray matter volume in the cingulate cortex in the AN patients, bilaterally. CONCLUSIONS: We argue that in spite of various known changes in the hypothalamus the direct hypothalamic response to glucose intake is similar in AN patients and healthy controls.

Longitudinal metabolite changes in Huntington's disease during disease onset.

BACKGROUND: Previous cross-sectional magnetic resonance spectroscopy (MRS) studies in Huntington's disease (HD) have demonstrated differences in metabolite concentrations in several regions of interest, especially the putamen and caudate nucleus. OBJECTIVE: To assess metabolite changes in both premanifest and early HD over a two year follow up period using MRS at 7 Tesla in several regions of interest. METHODS: In 13 HD gene carriers (10 premanifest and 3 manifest HD) proton MRS was performed at baseline and after 24 months. At follow up, four of the premanifest HD gene carriers had progressed into manifest HD, as assessed by clinical measures. 7T MR proton spectroscopy was performed in three regions of interest; the caudate nucleus, putamen and prefrontal cortex. Six metabolites were quantified for each region at each time point. Statistical analysis was performed using Wilcoxon signed rank tests. RESULTS: Across all subjects, a longitudinal decrease in the caudate nucleus in creatine (p = 0.038) and myo-inositol (p = 0.015) concentrations was found. A significant decrease in the putamen was seen in the total N-acetylaspartate (tNAA) (p = 0.028) and choline concentrations (p = 0.028). For premanifest HD converters, a non-significant high rate of tNAA decrease in the putamen was found compared to non-converting premanifest HD. CONCLUSION: Over a two year period we have demonstrated metabolite changes in the caudate nucleus and putamen of HD gene carriers around disease onset. This demonstrates the potential of MRS for providing a biomarker of disease progression and for evaluating future therapeutic interventions.