Gradient-recalled Echo MRI Research Articles

Association of obesity with cerebral microbleeds in neurologically asymptomatic elderly subjects

Obesity is associated with an increased risk of cardiovascular disease, but few studies have investigated the effects of obesity on subclinical cerebrovascular disease. Cerebral microbleeds (CMBs) are radiological markers of cerebral small vessel disease and reflect underlying vasculopathy. In this context, we assessed whether obesity was related to CMBs and to CMB subtypes categorized by location. Neurologically asymptomatic elderly subjects (n = 1,251; age ≥ 65 years) who visited for routine health check-ups were included in this study. Cerebral microbleeds were evaluated through T2*-weighted gradient-recalled echo MRI. The subjects were categorized into two groups depending on CMB location: strictly lobar and deep or infratentorial microbleeds. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria. A total of 120 (9.6 %) subjects were found to have CMBs. As the severity of obesity increased, the prevalence of CMBs increased. Compared with the normal weight group and after controlling possible confounders, the risk of deep or infratentorial microbleeds was significantly increased in the overweight group [odds ratio (OR) 2.32, 95 % confidence interval (CI) 1.19-4.53], and the obese group (OR 2.17, 95 % CI 1.14-4.13). However, the ORs for the strictly lobar microbleeds were not increased in either the overweight or obese groups. Obesity was associated with deep or infratentorial microbleeds. This finding suggests that obesity affects cerebral small vessels through arteriosclerotic vasculopathy. Based on our findings, we postulate that obesity is associated with the presence of subclinical and bleeding-prone cerebrovascular disease in the elderly.

Abstract 3208: Sensitivity and Reliability of SWI Compared to T2* GRE MRI for Detection of Microbleeds in Cerebral Amyloid Angiopathy

Introduction: Case examples and small case series suggest that MRI susceptibility weighted imaging (SWI) may be more sensitive for cerebral microbleed (CMB) detection compared to MRI T2* gradient-recalled echo (GRE). However, there are few data on CMB counts measured by SWI vs. GRE, or inter-rater reliability, in groups of patients with cerebral small vessel disease. We used data from a prospective cohort study of cerebral amyloid angiopathy (CAA), a cerebral small-vessel disease marked by high numbers of CMBs, to quantify the sensitivity and reliability of SWI vs. GRE for CMB detection. Methods: Nine patients with symptomatic CAA (mean age 71±8.3; 7 males and 2 females) and 21 healthy non-CAA controls (mean age 68±6.3; 10 M/11 F) underwent T2* GRE and SWI on a 3.0T MR scanner. Probable CAA was diagnosed according to the Boston criteria prior to study entry using information from clinical MRI with GRE sequences. Two raters (labeled 1 and 2) independently interpreted the GRE and SWI scans blinded to clinical information. The phase-filtered magnitude image was used for SWI interpretation. Agreement reliability was assessed using the kappa coefficient (where a kappa of ≥0.60 indicates good agreement) or the intraclass correlation coefficient (ICC). Results: Overall, the raters identified 1,432 CMBs in the 9 CAA cases (range 1-434 per patient) and 8 CMBs in the healthy controls (range 0-3). Rater 1 identified CMBs in 5/21 healthy controls on SWI and 5/21 on GRE, while rater 2 identified CMBs in 4/21 on SWI and 3/21 on GRE (kappa 0.70 for GRE and 0.57 for SWI). In CAA cases more CMBs were seen on SWI compared to the GRE sequence but the difference was significant only for rater 1 (rater 1: on average 85% more per patient on SWI than on GRE, p=0.008; rater 2: 19% more, p=0.25). Among CAA cases the reliability between raters was poor for GRE (ICC 0.36) but excellent for SWI (0.94, p<0.05 for comparison with GRE). Review suggested that the differing reliability was because rater 1 was less likely than rater 2 to identify faint lesions on GRE as CMB, whereas these lesions were more conspicuous on SWI. If SWI rather than GRE were used to determine CAA status according to the Boston criteria, all 9 CAA cases would remain classified as probable CAA but 2/21 controls would be reclassified as either possible (n=1) or probable (n=1) asymptomatic CAA based on the detection of one or more lobar microbleeds on SWI. Conclusions: SWI confers greater reliability as well as greater sensitivity for CMB detection compared to GRE, and should be the preferred sequence for quantifying CMBs. SWI may more frequently identify lobar microbleeds that could represent asymptomatic CAA. Further research is needed to determine whether the Boston criteria require revision to take into account the greater sensitivity of SWI for CMB detection.

Cerebral microhemorrhage and brain β-amyloid in aging and Alzheimer disease

Incidental cerebral microhemorrhage (MH) is frequently found in older individuals scanned with susceptibility-weighted MRI (SWI) or gradient-recalled echo MRI. MH have been linked with β-amyloid (Aβ) deposition using (11)C-Pittsburgh compound B (PiB) PET in Alzheimer disease (AD) and cerebral amyloid angiopathy (CAA). We hypothesized that Aβ deposition in asymptomatic elderly individuals is associated with lobar MH (LMH). This was a cross-sectional study of 84 elderly healthy controls (HC), 28 subjects with mild cognitive impairment (MCI), and 26 subjects with probable AD who underwent 3-T SWI and (11)C-PiB PET. (11)C-PiB cortical binding was quantified normalized to cerebellar cortex (standardized uptake value ratio [SUVR]) and scans classified as positive (PiB+) or negative (PiB-) by visual inspection. MH were manually counted and categorized by region and as lobar or nonlobar. LMH were present in 30.8% of AD, 35.7% of MCI, and 19.1% of HC. The prevalence of LMH among PiB+ subjects was similar, regardless of clinical classification (AD 30.8%, MCI 38.9%, HC 41.4%, p > 0.7). HC with LMH had significantly higher mean neocortical SUVR (1.7 ± 0.5) than HC without LMH (1.3 ± 0.3, p ± 0.01). In HC, there was a positive correlation between number of LMH and SUVR, and between LMH and age. In HC, PiB+ (odds ratio [OR] 7.3, 95% confidence interval [CI] 1.6-33.7, p = 0.01) and age (OR 1.2, 95% CI 1.03-1.3, p = 0.02) both independently predicted the occurrence of LMH using logistic regression. Asymptomatic Aβ deposition in older adults is strongly associated with LMH.

Mapping the brain in type II diabetes: Voxel-based morphometry using DARTEL

To investigate the pattern of brain volume changes of the brain in patients with type II diabetes mellitus using voxel-based morphometry. Institutional ethics approval and informed consent were obtained. VBM based on the high resolution three-dimensional T1-weighted fast spoiled gradient recalled echo MRI images was obtained from 16 type II diabetes patients (mean age 61.2 years) and 16 normal controls (mean age 59.6 years). All images were spatially preprocessed using Diffeomorphic Anatomical Registration using Exponentiated Lie algebra (DARTEL) algorithm, and the DARTEL templates were made from 100 normal subjects. Statistical parametric mapping was generated using analysis of covariance (ANCOVA). An atrophy pattern of gray matter was seen in type II diabetes patients compared with controls that involved the right superior, middle, and inferior temporal gyri, right precentral gyrus, and left rolandic operculum region. The loss of white matter volume in type II diabetes mellitus was observed in right temporal lobe and left inferior frontal triangle region. ROI analysis revealed that the gray and white matter volume of right temporal lobe were significant lower in type II diabetes mellitus than that in controls (P<0.05). This work demonstrated that type II diabetes mellitus patients mainly exhibited gray and white matter atrophy in right temporal lobe, and this finding supported that type II diabetes mellitus could lead to subtle diabetic brain structural changes in patients without dementia or macrovascular complications.

Imaging of acute stroke

Brain imaging provides an objective basis for the clinical inferences that direct individual patient management in the acute stroke setting. A brain CT or MRI scan is required for all patients with suspected stroke or transient ischemic attack. Thrombolytic therapy is arguably the most important aspect of acute stroke management; however, most decisions in acute stroke do not relate to this treatment. Stroke imaging must, therefore, provide information beyond the presence or absence of intracranial hemorrhage (ICH) and early evidence of a large infarct. Noncontrast CT and gradient-recalled echo MRI show comparable accuracy in the diagnosis of acute ICH. Diffusion-weighted MRI is more sensitive than noncontrast CT for differentiation of acute ischemic stroke from nonstroke conditions. Combined multimodal parenchymal, perfusion and vascular imaging with CT or MRI has the potential to identify patients with an ischemic penumbra that might be appropriate for acute reperfusion therapies. MRI identifies a broader range of acute and chronic cerebrovascular pathologies than does CT and, hence, could aid decisions about acute intervention, in-hospital management, and secondary prevention. Here, we present an overview of the diagnostic information that clinicians might gain from CT and MRI in the setting of acute stroke, along with the advantages and disadvantages of these techniques.

Biophysical mechanisms of phase contrast in gradient echo MRI

Recently reported contrast in phase images of human and animal brains obtained with gradient-recalled echo MRI holds great promise for the in vivo study of biological tissue structure with substantially improved resolution. Herein we investigate the origins of this contrast and demonstrate that it depends on the tissue "magnetic architecture" at the subcellular and cellular levels. This architecture is mostly determined by the structural arrangements of proteins, lipids, non-heme tissue iron, deoxyhemoglobin, and their magnetic susceptibilities. Such magnetic environment affects/shifts magnetic resonance (MR) frequencies of the water molecules moving/diffusing in the tissue. A theoretical framework allowing quantitative evaluation of the corresponding frequency shifts is developed based on the introduced concept of a generalized Lorentzian approximation. It takes into account both tissue architecture and its orientation with respect to the external magnetic field. Theoretical results quantitatively explain frequency contrast between GM, WM, and CSF previously reported in motor cortex area, including the absence of the contrast between WM and CSF. Comparison of theory and experiment also suggests that in a normal human brain, proteins, lipids, and non-heme iron provide comparable contributions to tissue phase contrast; however, the sign of iron and lipid contributions is opposite to the sign of contribution from proteins. These effects of cellular composition and architecture are important for quantification of tissue microstructure based on MRI phase measurements. Also theory predicts the dependence of the signal phase on the orientation of WM fibers, holding promise as additional information for fiber tracking applications.

Development and Validation of a Simple Conversion Model for Comparison of Intracerebral Hemorrhage Volumes Measured on CT and Gradient Recalled Echo MRI

Gradient recalled echo MRI (GRE) has been shown to be as accurate as CT for the detection of acute intracerebral hemorrhage (ICH). However, because of the differences in the signal parameter being detected, apparent hemorrhage size is expected to vary by imaging modality, with GRE providing larger volumes attributable to susceptibility effects. Image data from patients participating in 3 ICH studies were retrospectively reviewed. Patients with acute ICH were included if (1) concurrent MRI and CT were performed within 72 hours of symptom onset, and (2) each modality was performed within 240 minutes of each other. ICH volumes were calculated using a semiautomated image analysis program. The least squares method was used to develop a conversion equation based on a linear regression of GRE volume on CT volume. Thirty-six patients met inclusion criteria. MRI was performed first in 18, CT first in 18. Mean hemorrhage volume was 25.2 cc (range 0.1 to 83.9 cc) on CT and 32.7 cc (range 0.1 to 98.7 cc) measured on GRE. A linear relationship defined by CT Volume=GRE Volume*0.8 (Spearman's correlation coefficient=0.992, P<0.001) was derived. Acute ICH volumes as measured on GRE pulse sequences are consistently larger than CT volumes. A simple mathematical conversion model has been developed: CT volume=0.8*GRE volume. This formula can be used in studies using both imaging modalities, across different studies, or to track ICH growth over time independent of imaging modality in an individual patient.

Optimal TE for SPIO-Enhanced Gradient-Recalled Echo MRI for the Detection of Focal Hepatic Lesions

The objective of our study was to determine the optimal TE for superparamagnetic iron oxide (SPIO)-enhanced gradient-recalled echo (GRE) MRI for the detection of focal hepatic lesions. Ferucarbotran-enhanced GRE sequences, performed on a 1.5-T MR system, were used to evaluate 131 lesions (38 hepatocellular carcinomas, 37 metastases, 21 hemangiomas, 7 cholangiocarcinomas, 15 cysts, and 13 miscellaneous lesions) at four different TEs: 9, 13.5, 18, and 22.5 milliseconds. The lesion-to-liver signal difference-to-noise ratio (SDNR) was compared among the four GRE sequences by paired Student's t tests and among lesion types by an independent samples Student's t test. The McNemar test was used to compare the sensitivity for the detection of focal hepatic lesions. Wilcoxon's signed rank test was used to compare the subjective lesion conspicuity. The SDNRs of lesions on GRE images obtained at a TE of 13.5 milliseconds (mean +/- SD, 60 +/- 24) were significantly (p < 0.001) higher than those at TEs of 9 (55 +/- 23), 18 (55 +/- 22), and 22.5 milliseconds (47 +/- 19). The SDNR was highest at a TE of 13.5 milliseconds for SPIO-uptake lesions and was comparable on images obtained with TEs of 18 and 13.5 milliseconds for non-SPIO-uptake lesions. The non-SPIO-uptake lesions showed a significantly higher SDNR than the SPIO-uptake lesions at a TE of 22.5 milliseconds (p = 0.007). The overall sensitivity for lesion detection was not significantly different among the four GRE sequences, and the subjective ratings of lesion conspicuity were comparable for images obtained using TEs of 8, 13.5, and 18 milliseconds, but the ratings of lesion conspicuity were significantly lower for images obtained using a TE of 22.5 milliseconds (p < 0.001). For ferucarbotran-enhanced MRI, lesion SDNR was highest on images obtained using a TE of 13.5 milliseconds, but the sensitivity and lesion conspicuity were comparable at TEs of 9 and 18 milliseconds. The SDNR of liver lesions varied according to the lesion's potential capability of taking up SPIO agents.

Regional Pattern of Increased Water Diffusivity in Hippocampus and Corpus Callosum in Mild Cognitive Impairment

Background: Corpus callosum atrophy possibly indicates neuronal degeneration in association cortex in Alzheimer’s disease (AD). Water diffusivity allows detecting physiological changes that probably occur earlier than structural shrinkage in cerebral regions during the development of AD. Objective: To simultaneously investigate the focal volumetric and early structural changes with apparent diffusion coefficient (ADC) of corpus callosum in mild cognitive impairment (MCI), and to explore the regional pattern of ADC increase in hippocampus and corpus callosum. Methods: Thirteen subjects with MCI and 13 healthy age-matched control subjects were studied. With three-dimensional volumetric spoiled gradient recalled echo MRI images, we measured the volume of hippocampus and corpus callosum. Using MRI-guided diffusion-weighted imaging analysis, we calculated ADCs from hippocampus and corpus callosum. Within the receiver-operation curve (ROC) statistical framework, areas under ROC curves from hippocampal and callosal ADCs were compared in differentiating between MCI and controls. Results: After normalization to intracranial volume, hippocampal, not callosal, volume was significantly reduced in MCI. ADC values were increased in hippocampus and corpus callosum in MCI. The extent of ADC increase was similar between hippocampus and corpus callosum. Conclusion: Alterations in water diffusivity may precede corpus callosum atrophy during the development of MCI. Diffusion changes might occur simultaneously in allocortex and neocortex in MCI.

Phase contrast MRI of myocardial 3D strain by encoding contiguous slices in a single shot.

Quantitative measurements of inherently three-dimensional (3D) cardiac strain and strain rate require 3D data; MRI provides uniquely high sensitivity to material strain by combining phase contrast with single-shot acquisition methods, such as echo-planar imaging (EPI). Previous MRI methods applied to 3D strain used multiple two-dimensional (2D) acquisitions and suffered loss of sensitivity due to magnification within the strain calculation of physiologic noise related to cardiac beat-to-beat variability. In the present work, each single-shot acquisition generates 3D image data by acquiring two contiguous 2D Fourier transform (FT) images in a single echo train of an EPI readout. Although strain encoding divides across multiple EPI shots, each strain component is computed only within single-shot data, avoiding noise magnification. Strain tensor maps are displayed using iconic 3D graphics or a simple color code of tensor shape. In a deforming gel phantom, gradient-recalled echo (GRE) MRI movies of 3D strain rates match expected strain fields. In normal human subjects, 3D strain rate tensor movies of heart and brain comprising seven slices in each of seven cardiac phases were completed in 56 heartbeats. Stimulated echo (STE) MRI of net systolic 3D strain was also demonstrated. Two-slices-in-one-shot spatial encoding permits a complete quantitative survey of ventricular 3D strain in under a minute, with routine patient supervision and turnkey image processing.

MRI volumes of amygdala and hippocampus in non-mentally retarded autistic adolescents and adults.

To determine whether volumes of hippocampus and amygdala are abnormal in people with autism. Neuropathologic studies of the limbic system in autism have found decreased neuronal size, increased neuronal packing density, and decreased complexity of dendritic arbors in hippocampus, amygdala, and other limbic structures. These findings are suggestive of a developmental curtailment in the maturation of the neurons and neuropil. Measurement of hippocampus, amygdala, and total brain volumes from 1.5-mm coronal, spoiled gradient-recalled echo MRI scans in 14 non-mentally retarded autistic male adolescents and young adults and 14 individually matched, healthy community volunteers. Amygdala volume was significantly smaller in the autistic subjects, both with (p = 0.006) and without (p = 0.01) correcting for total brain volume. Total brain volume and absolute hippocampal volume did not differ significantly between groups, but hippocampal volume, when corrected for total brain volume, was significantly reduced (p = 0.04) in the autistic subjects. There is a reduction in the volume of amygdala and hippocampus in people with autism, particularly in relation to total brain volume. The histopathology of autism suggests that these volume reductions are related to a reduction in dendritic tree and neuropil development, and likely reflect the underdevelopment of the neural connections of limbic structures with other parts of the brain, particularly cerebral cortex.

Rapid monitoring of diffusion, DC potential, and blood oxygenation changes during global ischemia. Effects of hypoglycemia, hyperglycemia, and TTX.

The increasing interest in diffusion-weighted MRI (MRI) for diagnosis and monitoring of acute stroke in humans calls for a sound understanding of the underlying mechanisms of this image contrast in acute cerebral ischemia. The present study aimed to show that a rapid decrease in brain-water apparent diffusion coefficient (ADC) occurs coincident with anoxic depolarization and that this change is delayed by hyperglycemia and sodium channel blockade but accelerated by hypoglycemia. Rats were divided into groups: normoglycemic, hypoglycemic, and hyperglycemic, and those given local tetrodotoxin (TTX) application. Cardiac arrest was effected by intravenous KCl injection during serial high-speed diffusion and blood oxygenation-sensitive gradient-recalled echo MRI. Brain DC potential was recorded simultaneously. Serial ADC maps were calculated from the diffusion-weighted data and fitted to a model function to measure the delay between cardiac arrest and rapid ADC decrease. The time of anoxic depolarization indicated by DC change agreed well with the rapid drop in ADC in all groups; both were accelerated with hypoglycemia and delayed by hyperglycemia. A more gradual ADC decline occurred before anoxic depolarization, which was more pronounced in hyperglycemic animals and less pronounced in hypoglycemic animals. Rapid drop in ADC was also delayed by local TTX application. Changes in gradient-recalled echo image intensity were not significantly different among groups. While much of the ADC decrease in ischemia occurs during anoxic depolarization, significant but gradual ADC changes occur earlier that may not be due to a massive loss in ion homeostasis.

Modification of Tumour Perfusion and Oxygenation Monitored by Gradient Recalled Echo MRI and 31P MRS

Gradient recalled echo (GRE) 1H images can be used to monitor changes in blood oxygenation via the dephasing effects of paramagnetic deoxyhaemoglobin (Hb). We have modulated the blood flow/oxygenation of GH3 rat tumours by i.v. calcitonin gene-related peptide (CGRP) or carbogen (95% O2, 5% CO2) inhalation, and obtained GRE 1H images interleaved with 31P spectra before, during and after the insult. With CGRP the GRE image intensity decreased (6/10) by >10% with a concomitant 40% decrease (4/4) in βNTP/Pi and a small decrease in pH. Both the image intensity and 31P spectra returned to near their pre-CGRP levels after 50 min, consistent with a transient episode of hypoxia. Carbogen breathing (5/5) caused >40% increases in average GRE image intensity, with no significant changes in the 31P spectra (4/4). Three-dimensional GRE images were obtained to confirm that a T2* increase, rather than just an "in-flow' effect due to increased blood flow, was responsible for the GRE enhancement. Increases in average image intensity >40% were observed for the three-dimensional GRE images (2/2), indicating a T2* increase. Using Hb as an endogenous contrast agent, the high sensitivity of the GRE technique may provide a method of monitoring heterogeneous tumour perfusion and oxygenation, both in the laboratory and the clinic.

Modification of tumour perfusion and oxygenation monitored by gradient recalled echo MRI and 31P MRS.

Gradient recalled echo (GRE) 1H images can be used to monitor changes in blood oxygenation via the dephasing effects of paramagnetic deoxyhaemoglobin (Hb). We have modulated the blood flow/oxygenation of GH3 rat tumours by i.v. calcitonin gene-related peptide (CGRP) or carbogen (95% O2, 5% CO2) inhalation, and obtained GRE 1H images interleaved with 31P spectra before, during and after the insult. With CGRP the GRE image intensity decreased (6/10) by > 10% with a concomitant 40% decrease (4/4) in beta NTP/P1 and a small decrease in pH. Both the image intensity and 31P spectra returned to near their pre-CGRP levels after 50 min, consistent with a transient episode of hypoxia. Carbogen breathing (5/5) caused > 40% increases in average GRE image intensity, with no significant changes in the 31P spectra (4/4). Three-dimensional GRE images were obtained to confirm that a T2* increase, rather than just an 'in-flow' effect due to increased blood flow, was responsible for the GRE enhancement. Increases in average image intensity > 40% were observed for the three-dimensional GRE images (2/2), indicating a T2* increase. Using Hb as an endogenous contrast agent, the high sensitivity of the GRE technique may provide a method of monitoring heterogeneous tumour perfusion and oxygenation, both in the laboratory and the clinic.

Mapping drug-induced changes in cerebral R2* by Multiple Gradient Recalled Echo functional MRI.

A multiple Gradient Recalled Echo MRI sequence was used to map spatial and temporal changes in the rate of MR signal decay (R2*) in response to L-3,4-dihydroxyphenylalanine (levodopa) in the striatal dopaminergic system of a rhesus monkey unilaterally lesioned with 4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). R2* decreased significantly in the right (dopamine depleted) putamen and caudate following levodopa. More focal areas of smaller R2* decline were also observed in these structures in the left hemisphere. The observed spatial and temporal patterns of R2* change support the view that the method is monitoring changes in neural activity.