Are Dynamic Arterial Spin-Labeling MRA and Time-Resolved Contrast-Enhanced MRA Suited for Confirmation of Obliteration following Gamma Knife Radiosurgery of Brain Arteriovenous Malformations?

BACKGROUND AND PURPOSE: Intra-arterial DSA has been traditionally used for confirmation of cure following gamma knife radiosurgery for AVMs. Our aim was to evaluate whether 4D arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination can be an alternative to DSA for confirmation of AVM obliteration following gamma knife radiosurgery. MATERIALS AND METHODS: In this prospective study, 30 patients undergoing DSA for confirmation of obliteration following gamma knife radiosurgery for AVMs (criterion standard) also underwent MRA, including arterial spin-labeling MRA and contrast-enhanced time-resolved MRA. One dataset was technically unsatisfactory, and the case was excluded. The DSA and MRA datasets of 29 patients were independently and blindly evaluated by 2 observers regarding the presence/absence of residual AVMs. RESULTS: The mean time between gamma knife radiosurgery and follow-up DSA/MRA was 53 months (95% CI, 42-64 months; range, 22-168 months). MRA total scanning time was 9 minutes and 17 seconds. Residual AVMs were detected on DSA in 9 subjects (obliteration rate = 69%). All residual AVMs were detected on at least 1 MRA sequence. Arterial spin-labeling MRA and contrast-enhanced time-resolved MRA showed excellent specificity and positive predictive values individually (100%). However, their sensitivity and negative predictive values were suboptimal due to 1 false-negative with arterial spin-labeling MRA and 2 with contrast-enhanced time-resolved MRA (sensitivity = 88% and 77%, negative predictive values = 95% and 90%, respectively). Both sensitivity and negative predictive values increased to 100% if a composite assessment of both MRA sequences was performed. Diagnostic accuracy (receiver operating characteristic) and agreement (κ) are maximized using arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination (area under receiver operating characteristic curve = 1, P < .001; κ = 1, P < .001, respectively). CONCLUSIONS: Combining arterial spin-labeling MRA with contrast-enhanced time-resolved MRA holds promise as an alternative to DSA for confirmation of obliteration following gamma knife radiosurgery for brain AVMs, having provided 100% sensitivity and specificity in the study. Their combined use also enables reliable characterization of residual lesions.

MRI and pathology correlations in the medulla in sudden unexpected death in epilepsy (SUDEP): a postmortem study.

AIMS: Sudden unexpected death in epilepsy (SUDEP) likely arises as a result of autonomic dysfunction around the time of a seizure. In vivo MRI studies report volume reduction in the medulla and other brainstem autonomic regions. Our aim, in a pathology series, is to correlate regional quantitative features on 9.4T MRI with pathology measures in medullary regions. METHODS: Forty-seven medullae from 18 SUDEP, 18 nonepilepsy controls and 11 epilepsy controls were studied. In 16 cases, representing all three groups, ex vivo 9.4T MRI of the brainstem was carried out. Five regions of interest (ROI) were delineated, including the reticular formation zone (RtZ), and actual and relative volumes (RV), as well as T1, T2, T2* and magnetization transfer ratio (MTR) measurements were evaluated on MRI. On serial sections, actual and RV estimates using Cavalieri stereological method and immunolabelling indices for myelin basic protein, synaptophysin and Microtubule associated protein 2 (MAP2) were carried out in similar ROI. RESULTS: Lower relative RtZ volumes in the rostral medulla but higher actual volumes in the caudal medulla were observed in SUDEP (P < 0.05). No differences between groups for T1, T2, T2* and MTR values in any region was seen but a positive correlation between T1 values and MAP2 labelling index in RtZ (P < 0.05). Significantly lower MAP2 LI were noted in the rostral medulla RtZ in epilepsy cases (P < 0.05). CONCLUSIONS: Rostro-caudal alterations of medullary volume in SUDEP localize with regions containing respiratory regulatory nuclei. They may represent seizure-related alterations, relevant to the pathophysiology of SUDEP.

A visual quality control scale for clinical arterial spin labeling images.

BACKGROUND: Image-quality assessment is a fundamental step before clinical evaluation of magnetic resonance images. The aim of this study was to introduce a visual scoring system that provides a quality control standard for arterial spin labeling (ASL) and that can be applied to cerebral blood flow (CBF) maps, as well as to ancillary ASL images. METHODS: The proposed image quality control (QC) system had two components: (1) contrast-based QC (cQC), describing the visual contrast between anatomical structures; and (2) artifact-based QC (aQC), evaluating image quality of the CBF map for the presence of common types of artifacts. Three raters evaluated cQC and aQC for 158 quantitative signal targeting with alternating radiofrequency labelling of arterial regions (QUASAR) ASL scans (CBF, T1 relaxation rate, arterial blood volume, and arterial transient time). Spearman correlation coefficient (r), intraclass correlation coefficients (ICC), and receiver operating characteristic analysis were used. RESULTS: Intra/inter-rater agreement ranged from moderate to excellent; inter-rater ICC was 0.72 for cQC, 0.60 for aQC, and 0.74 for the combined QC (cQC + aQC). Intra-rater ICC was 0.90 for cQC; 0.80 for aQC, and 0.90 for the combined QC. Strong correlations were found between aQC and CBF maps quality (r = 0.75), and between aQC and cQC (r = 0.70). A QC score of 18 was optimal to discriminate between high and low quality clinical scans. CONCLUSIONS: The proposed QC system provided high reproducibility and a reliable threshold for discarding low quality scans. Future research should compare this visual QC system with an automatic QC system.

Hybrid MR-PET of brain tumours using amino acid PET and chemical exchange saturation transfer MRI.

PURPOSE: PET using radiolabelled amino acids has become a promising tool in the diagnostics of gliomas and brain metastasis. Current research is focused on the evaluation of amide proton transfer (APT) chemical exchange saturation transfer (CEST) MR imaging for brain tumour imaging. In this hybrid MR-PET study, brain tumours were compared using 3D data derived from APT-CEST MRI and amino acid PET using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET). METHODS: Eight patients with gliomas were investigated simultaneously with 18F-FET PET and APT-CEST MRI using a 3-T MR-BrainPET scanner. CEST imaging was based on a steady-state approach using a B1 average power of 1µT. B0 field inhomogeneities were corrected a Prametric images of magnetisation transfer ratio asymmetry (MTRasym) and differences to the extrapolated semi-solid magnetisation transfer reference method, APT# and nuclear Overhauser effect (NOE#), were calculated. Statistical analysis of the tumour-to-brain ratio of the CEST data was performed against PET data using the non-parametric Wilcoxon test. RESULTS: A tumour-to-brain ratio derived from APT# and 18F-FET presented no significant differences, and no correlation was found between APT# and 18F-FET PET data. The distance between local hot spot APT# and 18F-FET were different (average 20 ± 13 mm, range 4-45 mm). CONCLUSION: For the first time, CEST images were compared with 18F-FET in a simultaneous MR-PET measurement. Imaging findings derived from18F-FET PET and APT CEST MRI seem to provide different biological information. The validation of these imaging findings by histological confirmation is necessary, ideally using stereotactic biopsy.

A neuroradiologist's guide to arterial spin labeling MRI in clinical practice.

Arterial spin labeling (ASL) is a non-invasive MRI technique to measure cerebral blood flow (CBF). This review provides a practical guide and overview of the clinical applications of ASL of the brain, as well its potential pitfalls. The technical and physiological background is also addressed. At present, main areas of interest are cerebrovascular disease, dementia and neuro-oncology. In cerebrovascular disease, ASL is of particular interest owing to its quantitative nature and its capability to determine cerebral arterial territories. In acute stroke, the source of the collateral blood supply in the penumbra may be visualised. In chronic cerebrovascular disease, the extent and severity of compromised cerebral perfusion can be visualised, which may be used to guide therapeutic or preventative intervention. ASL has potential for the detection and follow-up of arteriovenous malformations. In the workup of dementia patients, ASL is proposed as a diagnostic alternative to PET. It can easily be added to the routinely performed structural MRI examination. In patients with established Alzheimer's disease and frontotemporal dementia, hypoperfusion patterns are seen that are similar to hypometabolism patterns seen with PET. Studies on ASL in brain tumour imaging indicate a high correlation between areas of increased CBF as measured with ASL and increased cerebral blood volume as measured with dynamic susceptibility contrast-enhanced perfusion imaging. Major advantages of ASL for brain tumour imaging are the fact that CBF measurements are not influenced by breakdown of the blood-brain barrier, as well as its quantitative nature, facilitating multicentre and longitudinal studies.

Arterial Spin-Labeling Parameters Influence Signal Variability and Estimated Regional Relative Cerebral Blood Flow in Normal Aging and Mild Cognitive Impairment: FAIR versus PICORE Techniques.

BACKGROUND AND PURPOSE: Arterial spin-labeling is a noninvasive method to map cerebral blood flow, which might be useful for early diagnosis of neurodegenerative diseases. We directly compared 2 arterial spin-labeling techniques in healthy elderly controls and individuals with mild cognitive impairment. MATERIALS AND METHODS: This prospective study was approved by the local ethics committee and included 198 consecutive healthy controls (mean age, 73.65 ± 4.02 years) and 43 subjects with mild cognitive impairment (mean age, 73.38 ± 5.85 years). Two pulsed arterial spin-labeling sequences were performed at 3T: proximal inversion with a control for off-resonance effects (PICORE) and flow-sensitive alternating inversion recovery technique (FAIR). Relative cerebral blood flow maps were calculated by using commercial software and standard parameters. Data analysis included spatial normalization of gray matter-corrected relative CBF maps, whole-brain average, and voxelwise comparison of both arterial spin-labeling sequences. RESULTS: Overall, FAIR yielded higher relative CBF values compared with PICORE (controls, 32.7 ± 7.1 versus 30.0 ± 13.1 mL/min/100 g, P = .05; mild cognitive impairment, 29.8 ± 5.4 versus 26.2 ± 8.6 mL/min/100 g, P < .05; all, 32.2 ± 6.8 versus 29.3 ± 12.3 mL/min/100 g, P < .05). FAIR had lower variability (controls, 36.2% versus 68.8%, P < .00001; mild cognitive impairment, 18.9% versus 22.9%, P < .0001; all, 34.4% versus 64.9% P < .00001). The detailed voxelwise analysis revealed a higher signal for FAIR, notably in both convexities, while PICORE had higher signal predominantly in deep cerebral regions. CONCLUSIONS: Overall, FAIR had higher estimated relative CBF and lower interindividual variability than PICORE. In more detail, there were regional differences between both arterial spin-labeling sequences. In summary, these results highlight the need to calibrate arterial spin-labeling sequences.

In vivo imaging of tau pathology using multi-parametric quantitative MRI.

As the number of people diagnosed with Alzheimer's disease (AD) reaches epidemic proportions, there is an urgent need to develop effective treatment strategies to tackle the social and economic costs of this fatal condition. Dozens of candidate therapeutics are currently being tested in clinical trials, and compounds targeting the aberrant accumulation of tau proteins into neurofibrillary tangles (NFTs) are the focus of substantial current interest. Reliable, translatable biomarkers sensitive to both tau pathology and its modulation by treatment along with animal models that faithfully reflect aspects of the human disease are urgently required. Magnetic resonance imaging (MRI) is well established as a valuable tool for monitoring the structural brain changes that accompany AD progression. However the descent into dementia is not defined by macroscopic brain matter loss alone: non-invasive imaging measurements sensitive to protein accumulation, white matter integrity and cerebral haemodynamics probe distinct aspects of AD pathophysiology and may serve as superior biomarkers for assessing drug efficacy. Here we employ a multi-parametric array of five translatable MRI techniques to characterise the in vivo pathophysiological phenotype of the rTg4510 mouse model of tauopathy (structural imaging, diffusion tensor imaging (DTI), arterial spin labelling (ASL), chemical exchange saturation transfer (CEST) and glucose CEST). Tau-induced pathological changes included grey matter atrophy, increased radial diffusivity in the white matter, decreased amide proton transfer and hyperperfusion. We demonstrate that the above markers unambiguously discriminate between the transgenic group and age-matched controls and provide a comprehensive profile of the multifaceted neuropathological processes underlying the rTg4510 model. Furthermore, we show that ASL and DTI techniques offer heightened sensitivity to processes believed to precede detectable structural changes and, as such, provides a platform for the study of disease mechanisms and therapeutic intervention.

Simulating NIRS and MRS measurements during cerebral hypoxia-ischaemia in piglets using a computational model.

We present a group analysis of the changes in cerebral haemodynamics, and the oxidation state of cytochrome-c-oxidase measured using broadband near-infrared spectroscopy (NIRS) and intracellular pH measured by phosphorous ((31)P) magnetic resonance spectroscopy (MRS) during and after cerebral hypoxia-ischaemia (HI) in 15 piglets. We use a previously published computational model of cerebral metabolism in the piglet [1] to integrate these measurements and simulate HI. We successfully simulate changes in cellular metabolism including shifts in intracellular pH observed in the piglet brain during HI. In this process, we optimise physiological parameters in the model identified through sensitivity analysis (such as the rate of glucose metabolism and intracellular lactate concentration), to fit simulated and measured data. The model fits the data reasonably and suggests a 20 % drop in glucose consumption, a ~65 % increase in lactate concentration and ~35 % drop in the cerebral metabolic rate of oxygen (CMRO2) during HI.

Brain mitochondrial oxidative metabolism during and after cerebral hypoxia-ischemia studied by simultaneous phosphorus magnetic-resonance and broadband near-infrared spectroscopy.

BACKGROUND: Multimodal measurements combining broadband near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy ((31)P MRS) assessed associations between changes in the oxidation state of cerebral mitochondrial cytochrome-c-oxidase (Δ[oxCCO]) and (31)P metabolite peak-area ratios during and after transient cerebral hypoxia-ischemia (HI) in the newborn piglet. METHODS: Twenty-four piglets (aged<24 h) underwent transient HI (inspired oxygen fraction 9% and bilateral carotid artery occlusion for ~20 min). Whole-brain (31)P MRS and NIRS data were acquired every minute. Inorganic phosphate (Pi)/epp, phosphocreatine (PCr)/epp, and total nucleotide triphosphate (NTP)/epp were measured by (31)P MRS and were plotted against Δ[oxCCO] during HI and recovery (epp=exchangeable phosphate pool=Pi+PCr+2γ-NTP+ß-NTP). RESULTS: During HI Δ[oxCCO], PCr/epp and NTP/epp declined and Pi/epp increased. Significant correlations were seen between (31)P ratios and Δ[oxCCO]; during HI a threshold point was identified where the relationship between Δ[oxCCO] and both NTP/epp and Pi/epp changed significantly. Outcome at 48 h related to recovery of Δ[oxCCO] and (31)P ratios 1h post-HI (survived: 1-h NTP/epp 0.22 ± 0.02, Δ[oxCCO] -0.29 ± 0.50 µM; died: 1-h NTP/epp 0.10 ± 0.04, Δ[oxCCO] -2.41 ± 1.48 µM). CONCLUSIONS: Both lowered Δ[oxCCO] and NTP/epp 1h post-HI indicated mitochondrial impairment. Animals dying before 48 h had slower recovery of both Δ[oxCCO] and (31)P ratios by 1 h after HI.

Correcting radiofrequency inhomogeneity effects in skeletal muscle magnetisation transfer maps.

The potential of MRI to provide quantitative measures of neuromuscular pathology for use in therapeutic trials is being increasingly recognised. Magnetisation transfer (MT) imaging shows particular promise in this context, being sensitive to pathological changes, particularly in skeletal muscle, where measurements correlate with clinically measured muscle strength. Radiofrequency (RF) transmit field (B(1)) inhomogeneities can be particularly problematic in measurements of the MT ratio (MTR) and may obscure genuine muscle MTR changes caused by disease. In this work, we evaluate, for muscle imaging applications, a scheme previously proposed for the correction of RF inhomogeneity artefacts in cerebral MTR maps using B(1) information acquired in the same session. We demonstrate the theoretical applicability of this scheme to skeletal muscle using a two-pool model of pulsed quantitative MT. The correction scheme is evaluated practically in MTR imaging of the lower limbs of 28 healthy individuals and in two groups of patients with representative neuromuscular diseases: Charcot-Marie-Tooth disease type 1A and inclusion body myositis. The correction scheme was observed to reduce both the within-subject and between-subject variability in the calf and thigh muscles of healthy subjects and patient groups in histogram- and region-of-interest-based approaches. This method of correcting for RF inhomogeneity effects in MTR maps using B(1) data may markedly improve the sensitivity of MTR mapping indices as measures of pathology in skeletal muscle.

MR regional perfusion imaging: visualizing functional collateral circulation.

SUMMARY: We applied regional perfusion imaging (RPI), a new arterial spin-labeling MR imaging method that selectively studies regions of the brain perfused by individual carotid and basilar arteries. In a patient with cerebrovascular disease, RPI showed cerebral tissue perfused by pial collateral vessels, thereby demonstrating the relationship between anatomic and functional information, which was lacking in conventional x-ray angiography. RPI may be useful to study functional collateral circulation and hence guide therapy in ischemic disease.

Non-invasive measurement of perfusion: a critical review of arterial spin labelling techniques.

The non-invasive nature of arterial spin labelling (ASL) has opened a unique window into human brain function and perfusion physiology. High spatial and temporal resolution makes the technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience where the aim is to develop a more comprehensive picture of the physiological events accompanying neuronal activation. However, low signal-to-noise ratio and the complexity of flow quantification make ASL one of the more demanding disciplines within MRI. In this review, the theoretical background and main implementations of ASL are revisited. In particular, the perfusion quantification methods, including the problems and pitfalls involved, are thoroughly discussed in this article. Finally, a brief summary of applications is provided.

Early experiences with diffusion tensor imaging and magnetic resonance tractography in stroke patients.

INTRODUCTION: Recent advances in magnetic resonance (MR) diffusion tensor imaging technique enable evaluation of the anisotropy of white matter tracts in-vivo, as well as the integrity of fibre tracts and their orientation. We describe our initial experiences with diffusion tensor imaging and MR tractography techniques to evaluate the structural degeneration of white matter tracts following stroke. METHODS: Diffusion tensor imaging data were acquired in 11 cases with stroke on a 3T MR imaging scanner, with three-dimensional diffusion tensor imaging-based colour maps and MR tractography performed offline. We evaluated the spatial relationships of the eloquent white matter tracts to the infarcts and areas of haemorrhage, and classified therewith the tracts as either disrupted or displaced. We compared these with the clinical severity of the neurological deficits and prognosis. RESULTS: A good correlation was found between tractography findings and patient's clinical recovery. All the patients with disruption of white matter tracts had residual deficits on clinical follow-up, whereas the patients with displaced tracts had near complete neurological recovery. CONCLUSION: Diffusion tensor imaging and MR tractography provide a novel and useful method to directly visualise changes in the white matter tracts in stroke. This can potentially allow clinical-imaging correlation with prognostic potential.

Three-dimensional isotropic contrast-enhanced MR angiography of the carotid artery using sensitivity-encoding and random elliptic centric k-space filling: technique optimization.

We present a study that helped optimize a three-dimensional isotropic contrast-enhanced MR angiographic (CE-MRA) technique, using sensitivity encoding (SENSE) and random elliptic centric k-space filling. Two-dimensional gradient-echo sequence (TR/TE/flip angle 3.4/0.97/40 degrees ) was used to generate time-intensity curves in porcine carotid arteries for a fixed dose of Gd-DTPA (0.02 mmol/kg) at the following intravenous injection rates: 0.1, 0.3, 0.5, 1.0, 1.5, 2.0, and 3.0 ml/s. The time of contrast arrival and time to peak were recorded. Based on the time-intensity curves, three-dimensional high-resolution isotropic (1 mm3) CE-MRA sequence (TR/TE/flip angle: 4.9/2.4/30 degrees ), using SENSE (reduction factor of 2) and random elliptic centric k-space filling, was initiated twice for each of the above injection rates: first at the time of contrast arrival and second at the time of peak contrast. The three-dimensional CE-MRA images were analyzed for artifacts, signal-to-noise ratio, and venous contamination. For the three-dimensional CE-MRA acquisitions that were initiated at the time of contrast arrival, there was a gradual improvement in signal-to-noise ratio (SNR) in the carotid arteries with increasing injection rate. The same trend was not observed for the acquisitions that were initiated at the time of peak contrast. SENSE combined with random elliptic k-space acquisition in CE-MRA allows for higher SNR with fewer ringing artifacts at faster contrast injection rates.

Magnetization transfer MRI demonstrates spinal cord abnormalities in adrenomyeloneuropathy.

BACKGROUND: In adrenomyeloneuropathy (AMN) conventional MRI detects only spinal cord atrophy in the late stages. OBJECTIVE: To apply a magnetization transfer-weighted (MTw) imaging to patients with AMN and AMN-like syndrome in order to visualize and quantitatively assess the pathology of white matter tracts in the cervical spinal cord. METHODS: MTw studies were conducted in nine men with AMN, eight symptomatic heterozygous women, and 10 age- and sex-matched controls and compared to the Expanded Disability Status Scale (EDSS) and quantitative tests of vibratory sense and postural sway. MTw data sets were obtained at the level of C1 to C3 using a three-dimensional gradient echo acquisition technique, these images were then standardized between subjects by using the in-slice CSF signal as a normalization reference, allowing a quantitative assessment of the MTw signal. RESULTS: In contrast to conventional MRI, MTw images showed signal hyperintensities in the lateral and dorsal columns of all patients. The MT signal quantified in the dorsal column showed significant differences between patients with AMN, X-linked adrenoleukodystrophy heterozygotes, and controls. MT hyperintensity in the dorsal column correlated with EDSS, vibratory sense, and postural sway. CONCLUSION: Magnetization transfer-weighted imaging is a sensitive modality for the visual and quantitative assessment of spinal cord pathology in adrenomyeloneuropathy, and is a potential tool for evaluation of new therapies.

Application of regional perfusion imaging to extra-intracranial bypass surgery and severe stenoses.

Arterial Spin Labeling (ASL) is a non-invasive method to quantitatively measure perfusion without the need of contrast material. Measurement of perfusion is derived from the subtraction of two consecutively acquired scans, with or without radio frequency labeling of the magnetization in the feeding arteries. So far, almost all ASL methods only allowed labeling the entire feeding artery tree of the brain simultaneously, without separation of the individual perfusion territories. In this paper, we describe a newly developed method, Regional Perfusion Imaging, allowing quantitative measurement of perfusion in the watershed of individually labeled arteries (right and left internal carotids, as well as basilar artery and the posterior circulation). Unlike conventional digital subtraction angiography, this new method is completely non-invasive, and allows to selectively measure cerebral perfusion, and not only to get angiograms of the feeding vessels. Regional perfusion was already measured in more than 70 elderly healthy volunteers and over 30 patients with internal carotid disease (severe stenoses and/or after extra-intracranial bypass surgery). A large variation among perfusion territories, even in healthy volunteers, can be appreciated. This method has the potential to increase our understanding of the relationship between collateral flow and regional perfusion in patients with neurovascular diseases.

SENSE-DTI at 3 T.

While holding vast potential, diffusion tensor imaging (DTI) with single-excitation protocols still faces serious challenges. Limited spatial resolution, susceptibility to magnetic field inhomogeneity, and low signal-to-noise ratio (SNR) may be considered the most prominent limitations. It is demonstrated that all of these shortcomings can be effectively mitigated by the transition to parallel imaging technology and high magnetic field strength. Using the sensitivity encoding (SENSE) technique at 3 T, brain DTI was performed in nine healthy volunteers. Despite enhanced field inhomogeneity, parallel acquisition permitted both controlling geometric distortions and enhancing spatial resolution up to 0.8 mm in-plane. Heightened SNR requirements were met in part by high base sensitivity at 3 T. A further significant increase in SNR efficiency was accomplished by SENSE acquisition, exploiting enhanced encoding speed for echo time reduction. Based on the resulting image data, high-resolution tensor mapping is demonstrated.

Comparison of the dependence of blood R2 and R2* on oxygen saturation at 1.5 and 4.7 Tesla.

Gradient-echo (GRE) blood oxygen level-dependent (BOLD) effects have both intra- and extravascular contributions. To better understand the intravascular contribution in quantitative terms, the spin-echo (SE) and GRE transverse relaxation rates, R(2) and R(2)(*), of isolated blood were measured as a function of oxygenation in a perfusion system. Over the normal oxygenation saturation range of blood between veins, capillaries, and arteries, the difference between these rates, R'(2) = R(2)(*) - R(2), ranged from 1.5 to 2.1 Hz at 1.5 T and from 26 to 36 Hz at 4.7 T. The blood data were used to calculate the expected intravascular BOLD effects for physiological oxygenation changes that are typical during visual activation. This modeling showed that intravascular DeltaR(2)(*) is caused mainly by R(2) relaxation changes, namely 85% and 78% at 1.5T and 4.7T, respectively. The simulations also show that at longer TEs (>70 ms), the intravascular contribution to the percentual BOLD change is smaller at high field than at low field, especially for GRE experiments. At shorter TE values, the opposite is the case. For pure parenchyma, the intravascular BOLD signal changes originate predominantly from venules for all TEs at low field and for short TEs at high field. At longer TEs at high field, the capillary contribution dominates. The possible influence of partial volume contributions with large vessels was also simulated, showing large (two- to threefold) increases in the total intravascular BOLD effect for both GRE and SE.

Neuroimaging studies in Rett syndrome.

Neuroimaging is a key instrument for determining structural and in vivo functional status of the brain, non-invasively. Multiple approaches can now determine aspects of anatomic and neurochemical changes in brain, and have been utilized effectively in Rett Syndrome patients to understand the biological basis of this neurodevelopmental disorder. Studies performed at our institute include volumetric analyses of MRI, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), cerebral blood flow measurements with MRI, and positron emission tomography scans (PET). These studies have provided considerable insight into mechanisms underlying the clinical features of this disease. Volumetric analyses suggest that decreased brain volume in RS results from global reductions in both gray and white matter of the brain. A selective vulnerability of the frontal lobes is evidenced by the preferential reduction of blood flow, increased choline and reduced n-acetyl aspartate (NAA) by MRS, and increased glucose uptake in these same regions as shown by ((18)F)-fluorodeoxyglucose (FDG) PET scans. We hypothesize that the increased glucose uptake relates to increased glutamate cycling in synapses. The resulting neuroexcitotoxic injury to the developing brain contributes to the seizures, behavioral disturbance and respiratory irregularities commonly seen in phases 1 and 2 of this disorder.