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Biomedical subjects

M A Horsfield

Publications and source records attributed to M A Horsfield.

At least 19 recordsLinked to original sources

Pathologic damage in MS assessed by diffusion-weighted and magnetization transfer MRI.

OBJECTIVE: To compare diffusion characteristics of MS lesions, normal-appearing white matter (NAWM) from patients, and normal white matter from control subjects, and to investigate the correlations between the magnetization transfer ratio (MTR) and a directionally averaged tissue water diffusion coefficient (D) in patients. BACKGROUND: MS and other pathologic processes that modify tissue integrity can result in abnormal diffusion of water molecules detectable by diffusion-weighted imaging (DWI). METHODS: Conventional dual-echo and DWI scans were obtained from 35 patients with relapsing-remitting MS and 24 healthy control subjects. MT scans were also obtained from the patients. After coregistration of all scans, MTR and D values from MS lesions and NAWM in different regions were marked using the dual-echo scans as a reference. D values from the same brain regions in control subjects were acquired. Histograms of MTR and D were also produced. RESULTS: Patients with MS had significantly higher D values in all the areas studied. Moreover, histogram metrics (peak height, peak site, and average D) from patients were substantially different from those of control subjects. In patients, average lesion D and MTR were markedly different from those in the NAWM. There was an inverse correlation between average lesion MTR and D inside lesions, whereas no correlation was found for average MTR and D taken from the histograms. CONCLUSIONS: DWI detects severe tissue disruption inside lesions and subtle widespread abnormalities in NAWM in patients with relapsing-remitting MS. MT and DWI may provide information about different aspects of brain pathology in MS.

Adult↗

Imaging the cerebral hemispheres: technical issues.

The article discusses the current problems faced when applying magnetic resonance imaging to the cerebral hemispheres, and reviews the prospects for improvements in image quality. While this anatomical area does not present any difficulties that are peculiar to the region, it is the advanced techniques, such as diffusion-weighted imaging, functional magnetic resonance imaging and spectroscopy, often applied in the cerebrum that present the real challenges.

Brain↗

A conventional and magnetization transfer MRI study of the cervical cord in patients with MS.

OBJECTIVE: To evaluate the contribution made by cervical cord damage, assessed using a fast short-tau inversion recovery (fast-STIR) sequence and magnetization transfer ratio (MTR) histogram analysis to the clinical manifestations of MS. BACKGROUND: Previous studies have failed to show significant correlations between the number and extent of T2 spinal cord lesions and the clinical status of patients with MS. Fast-STIR is more sensitive than T2-weighted imaging for detecting cervical cord MS lesions. MTR histogram analysis provides estimates of the overall disease burden in the cervical cord with higher pathologic specificity to the more destructive aspects of MS than T2-weighted scans. METHODS: We obtained fast-STIR and magnetization transfer (MT) scans from 96 patients with MS (52 with relapsing-remitting [RRMS], 33 with secondary progressive [SPMS], and 11 with primary progressive [PPMS] MS) and 21 control subjects. Dual-echo scans of the brain were also obtained and lesion load measured. RESULTS: Eighty-one of the patients with MS had an abnormal cervical cord scan. Patients with SPMS had more cervical cord lesions and more images with visible cervical cord damage than did patients with RRMS or PPMS (p = 0.04). The entire cohort of patients with MS had lower average MTR of the cervical cord (p = 0.006) than control subjects. Compared to control subjects, patients with RRMS had similar cervical cord MTR histogram-derived measures, whereas those with PPMS had lower average MTR (p = 0.01) and peak height (p = 0.02). Patients with SPMS had lower histogram peak height than did those with RRMS (p = 0.03). The peak position and height of the cervical cord MTR histogram were independent predictors of the probability of having locomotor disability. We found no correlation between brain T2 lesion load and any of the cervical cord MTR histogram metrics. CONCLUSIONS: This study shows that the amount and severity of MS pathology in the cervical cord are greater in the progressive forms of the disease. An accurate assessment of cervical cord damage in MS gives information that can be used in part to explain the clinical manifestations of the disease.

Adult↗

Visualization of cranial nerves I-XII: value of 3D CISS and T2-weighted FSE sequences.

The aim of this study was to evaluate the sensitivity of the three-dimensional constructive interference of steady state (3D CISS) sequence (slice thickness 0.7 mm) and that of the T2-weighted fast spin echo (T2-weighted FSE) sequence (slice thickness 3 mm) for the visualization of all cranial nerves in their cisternal course. Twenty healthy volunteers were examined using the T2-weighted FSE and the 3D CISS sequences. Three observers evaluated independently the cranial nerves NI-NXII in their cisternal course. The rates for successful visualization of each nerve for 3D CISS (and for T2-weighted FSE in parentheses) were as follows: NI, NII, NV, NVII, NVIII 40 of 40 (40 of 40), NIII 40 of 40 (18 of 40), NIV 19 of 40 (3 of 40), NVI 39 of 40 (5 of 40), NIX, X, XI 40 of 40 (29 of 40), and NXII 40 of 40 (4 of 40). Most of the cranial nerves can be reliably assessed when using the 3D CISS and the T2-weighted FSE sequences. Increasing the spatial resolution when using the 3D CISS sequence increases the reliability of the identification of the cranial nerves NIII-NXII.

Adult↗

Activity revealed in MRI of multiple sclerosis without contrast agent. A preliminary report.

Disease activity in multiple sclerosis is usually accompanied by blood-brain barrier disruption, which can be assessed with contrast-enhanced magnetic resonance imaging (MRI). This paper describes a technique that gives information about disease activity using magnetization transfer MRI. Image combination methods using follow-up scans, like the one presented here, have the potential to show MS lesions that correlate with enhancement.

Blood-Brain Barrier↗

Contrast-reduced imaging of tissue concentration and arterial level (CRITICAL) for assessment of cerebral hemodynamics in acute stroke by magnetic resonance.

RATIONALE AND OBJECTIVES: To compare cerebral perfusion data obtained by using a low-dose, T1-weighted MRI technique with radionuclide (single positron emission computed tomography [SPECT]) brain imaging and to assess the reproducibility of parametric MRI data (cerebral blood flow [CBF], cerebral blood volume [CBV], and time to peak [TTP]) by applying a previously described nuclear medicine technique to derive quantitative perfusion data. METHODS: Single-slice brain and neck images were rapidly acquired during the passage of a small (1/10th of normal dose) bolus of contrast. Parametric images were constructed from the MR data by extracting the bolus transit curve for the brain and the peak arterial input curve from the carotid vessels in the neck. These were compared with SPECT perfusion imaging. Twenty-four patients with acute stroke were studied with both techniques; 13 underwent repeated scanning to assess data reproducibility. RESULTS: Relative CBF data were comparable to SPECT data (r = 0.584, P = 0.01). Results were reproducible for relative CBF, CBV, and TTP. The arterial input function was significantly different on the second injection with an average difference of 73.5, suggesting that the signal-concentration relationship had lost linearity with increased contrast load. Absolute quantitative MRI data produced values in the expected range (CBF = 42.6 mL x 100 g(-1) x min(-1)). CONCLUSIONS: This technique allows estimation of CBF in the setting of acute stroke with quantitative values in the expected range. Repeated measurements in the same patients showed that this technique provides a reproducible measure of relative CBF, CBV, and TTP.

Brain↗

Cluster analysis of diffusion tensor magnetic resonance images in human head injury.

OBJECTIVE: Issues surrounding the nature of the edema associated with traumatic brain injury in humans, and its evolution in the acute phase, remain unresolved. This study aimed to characterize the topographical nature of the pathophysiological changes in human traumatic brain injury with diffusion tensor magnetic resonance imaging. METHODS: Multislice diffusion-weighted magnetic resonance imaging data were acquired from five patients undergoing elective ventilation for management of traumatic focal contusion or hematomas. The diffusion tensor and the T2-weighted intensity were then computed for every voxel in the image data set for each patient. The topographical distribution of abnormalities in the trace of the diffusion tensor and T2-weighted images were characterized by cluster analysis. RESULTS: In four patients with technically satisfactory data, a narrow band of tissue was observed in the periphery of focal lesions, which was characterized by selective reduction in the trace of the diffusion tensor, without any associated increase in the T2-weighted signal intensity. CONCLUSION: This change is interpreted as indicating either a partial redistribution of water from the extra- to intracellular compartment, or a reduction in the diffusivity of water in the intracellular or cytosolic environment. These diffusion and T2-weighted characteristics are also found in early ischemic change, hence, such regions may represent potentially salvageable tissue at risk of permanent damage. The study illustrates the advantage of using information contained within the diffusion tensor in addition to more conventional imaging sequences.

Adolescent↗

Diffusion tensor MRI assesses corticospinal tract damage in ALS.

BACKGROUND: A number of neurophysiologic and neuroimaging techniques have been evaluated in the research setting to assess upper motor neuron (UMN) damage in ALS. Changes in tissue structure in the CNS modify the diffusional behavior of water molecules, which can be detected by diffusion tensor MRI. OBJECTIVES: To explore the hypothesis that degeneration of the motor fibers in ALS would be reflected by changes in the diffusion characteristics of the white matter fibers in the posterior limb of the internal capsule and that these changes could be detected by diffusion tensor MRI. METHODS: We studied 22 patients with El Escorial definite, probable, or possible ALS-11 with limb onset (mean age 54.5 +/- 10.7 years) and 11 with bulbar onset (mean age 49.6 +/- 11.7 years)-and compared them with 20 healthy, age-matched controls (mean age 46.0 +/- 12.6 years). We assessed central motor conduction time (CMCT), threshold to stimulation, and silent period using transcranial magnetic stimulation. Diffusion tensor MRI was performed using a 1.5-T GE Signa system (Milwaukee, WI) fitted with Advanced NMR hardware and software capable of producing echo planar MR images. Data were acquired from seven coronal slices centered to include the posterior limb of the internal capsule. Maps of the mean diffusivity, fractional anisotropy, and T2-weighted signal intensity were generated. RESULTS: There were no differences between the subject groups on measures of CMCT, threshold to stimulation, and silent period. However, the CMCT correlated with clinical measures of UMN involvement. We found a significant increase in the mean diffusivity and reduction in fractional anisotropy along the corticospinal tracts between the three subject groups, most marked in the bulbar-onset group. The fractional anisotropy correlated with measures of disease severity and UMN involvement, whereas the mean diffusivity correlated with disease duration. CONCLUSION: The results support the use of diffusion tensor MRI in detecting pathology of the corticospinal tracts in ALS.

Adult↗

Non-invasive assessment of axonal fiber connectivity in the human brain via diffusion tensor MRI.

A technique for assessing in vivo fiber connectivity in the human brain is presented. The method utilizes a novel connectivity algorithm that operates in three spatial dimensions and uses estimates of fiber tract orientation and tissue anisotropy, obtained from diffusion tensor magnetic resonance imaging, to establish the pathways of fiber tracts. Sample in vivo connectivity images from healthy human brain are presented that demonstrate connections in the white matter tracts. White matter connectivity information is potentially of interest in the study of a range of neurological, psychiatric, and developmental disorders and shows promise for following the natural history of disease.

Algorithms↗

An optimized pulse sequence for isotropically weighted diffusion imaging.

Single-shot echo-planar imaging is becoming the most widely used technique for magnetic resonance diffusion imaging, since it enables measurement of diffusion coefficients in human brain without motion artifacts. However, its reliability is limited by geometrical distortions due to eddy currents. In this report, an isotropically weighted echo-planar pulse sequence, optimized to give the maximum signal-to-noise ratio in the computed trace image and designed to produce inherently low distortions, is presented. It is also shown how the residual translational distortion can be easily characterized and removed by postprocessing. A full characterization of the distortion artifact involves a few measurements on a phantom, in order to estimate the distortion as a function of slice orientation, which can then be used to correct any slice orientation. Results of applying the image translation correction to data collected from a patient are presented.

Artifacts↗

Mapping eddy current induced fields for the correction of diffusion-weighted echo planar images.

Diffusion-weighted echo-planar magnetic resonance imaging is potentially of great importance as a diagnostic imaging tool; however, the technique currently suffers a number of limitations, including the image distortion caused by the eddy current induced fields when the diffusion-weighting magnetic field gradient pulses are applied. The distortions cause mis-registration between images with different diffusion-weighting, that then results in artifacts in quantitative diffusion images. A method is presented to measure the magnetic fields generated from the eddy currents for each of three orthogonal gradient pulse vectors, and then to use these to ascertain the image distortion that occurs in subsequent diffusion-weighted images with arbitrary gradient pulse vector amplitude and direction, and image plane orientation. The image distortion can then be reversed. Both temporal and spatial dependence of the residual eddy current induced fields are included in the analysis. Image distortion was substantially reduced by the correction scheme, for arbitrary slice position and angulation. This method of correction is unaffected by the changes in image contrast that occur due to diffusion weighting, and does not need any additional scanning time during the patient scan. It is particularly suitable for use with single-shot echo planar imaging.

Anisotropy↗

A myocardial perfusion reserve index in humans using first-pass contrast-enhanced magnetic resonance imaging.

OBJECTIVES: The purpose of this study was to evaluate a myocardial perfusion reserve index (MPRI) derived from a quantitative magnetic resonance imaging (MRI) technique in normal human volunteers and patients with coronary artery disease and to relate MPRI to coronary artery stenosis severity measured with quantitative arteriography. BACKGROUND: Magnetic resonance imaging could be a useful noninvasive tool in the investigation of ischemic heart disease. However, there have been few studies in humans to quantify myocardial perfusion and myocardial perfusion reserve using MRI and none in patients with coronary disease. METHODS: Twenty patients with angiographically proven coronary artery disease and five normal volunteers underwent both resting and stress (adenosine 140 microg/kg(-1)/min(-1)) first-pass contrast-enhanced MRI examinations (using 0.05 mmol/kg 1 of gadopentetate dimeglumine. Using a tracer kinetic model, the unidirectional transfer constant (K(i)), a perfusion marker for the myocardial uptake of contrast, was computed in each coronary arterial territory. The ratio of K(i) for the rest and stress scans was used to calculate the MPRI. Percent reduction in luminal diameter of coronary lesions was measured using an automated edge-detection algorithm. RESULTS: Myocardial perfusion reserve index was significantly reduced in patients compared with normal subjects (2.02+/-0.7 vs. 4.21+/-1.16, p < 0.02). For regions supplied by individual vessels, there was a significant negative correlation of MPRI with percent diameter stenosis (r = -0.81, p < 0.01). Importantly, regions supplied by vessels with <40% diameter stenosis (non-flow limiting) had a significantly higher MPRI than regions supplied by stenoses of "intermediate" severity, that is, >40% to 59% diameter stenosis (2.80+/-0.77 and 1.93+/-0.38, respectively, p < 0.02). However, even regions supplied by vessels with <40% diameter stenosis had a significantly lower MPRI than volunteers (p < 0.01). CONCLUSIONS: A myocardial perfusion reserve index derived from first-pass MRI studies can distinguish between normal subjects and patients with coronary artery disease. Furthermore, it provides useful functional information on coronary lesions, particularly where the physiologic significance cannot be predicted accurately from the angiogram.

Adenosine↗

Protein-ligand interactions measured by 15N-filtered diffusion experiments.

NMR diffusion coefficient measurements have been shown to be sensitive to the conformational and oligomeric states of proteins. Recently, heteronuclear-filtered diffusion experiments have been proposed [Dingley et al. (1997) J. Biomol. NMR, 10, 1-8]. Several new heteronuclear-filtered diffusion pulse sequences are proposed which are shown to have superior sensitivity to those previously proposed. One of these new heteronuclear-filtered diffusion experiments has been used to study the binding of an SH3 domain to a peptide. Using this system, we show that it is possible to measure binding constants from diffusion coefficient measurements.

Diffusion↗

Interferon beta treatment for multiple sclerosis has a graduated effect on MRI enhancing lesions according to their size and pathology.

OBJECTIVE: The ability of recombinant human interferon beta-1a (rh-IFN beta-1a) to suppress multiple sclerosis activity, evaluated from MRI, was assessed across a range of lesions enhancing at different gadolinium-DTPA (Gd) doses and with different sizes. METHODS: Every 4 weeks, standard dose (Sd; 0.1 mmol/kg Gd) and triple dose (Td; 0.3 mmol/kgGd) MRI were obtained from 18 patients with relapsing-remitting multiple sclerosis for 3 months before and 4 months after starting treatment with 44 microgram rh-IFN beta-1a subcutaneously, once a week. RESULTS: The total numbers of enhancing lesions were 145 and 126 on Sd scans and 278 and 192 on the Td scans obtained before and after treatment. The introduction of treatment decreased, on average, the rate of appearance of new enhancing lesions seen on Sd and Td scans by 37% (p<0.001). Treatment effects on new enhancing lesions seen on Td scans was, on average, 28% higher than on those seen on Sd scans. The distribution of lesion sizes on Td scans changed significantly during the treatment period (p=0.05), due to a marked decrease in the number of small lesions. CONCLUSIONS: The effect of 44 microgram rh-IFN beta-1a in reducing multiple sclerosis disease activity, as monitored by Gd enhanced MRI, is not homogeneous, but graduated according to the pathological characteristics and size of the lesions.

Adult↗

Interferon-beta-1a in relapsing-remitting multiple sclerosis: effect on hypointense lesion volume on T1 weighted images.

OBJECTIVE: Recently, a strong correlation between the increase in hypointense lesion load on T1 weighted spin echo images, and the increase in disability was reported. Although the effect of interferon-beta has been demonstrated both in reducing exacerbation rate, frequency of enhancing lesions, and accumulation of disease burden on T2 weighted images, the impact on the accumulation of hypointense lesions has not yet been evaluated. The aims of the present study were: (a) to assess for the first time the effect of interferon-beta-1a on T1 weighted MRI hypointense lesion volume; and (b) to evaluate the relation between changes on hypointense, hyperintense, and enhancing lesion volume before and during interferon-beta-1a treatment in relapsing-remitting multiple sclerosis. METHODS: After a baseline scan and 6 month pretreatment period, 67 patients with relapsing-remitting multiple sclerosis were treated with interferon-beta-1a by subcutaneous injection three times a week during a 12 month treatment period. All patients had MRI every month during the 6 month pretreatment period and for the first 9 months of the treatment period. A final MRI was also performed at the end of the 12 month treatment period. RESULTS: There was a significant increase in the mean hyperintense lesion volume during the pretreatment phase (6 months) and a slight decrease during the treatment period (12 months), whereas the hypointense lesion volume increased significantly before treatment and remained substantially stable during treatment. There was a significant correlation between changes in hypointense and hyperintense lesion volume during the observation period, but not during treatment. The monthly mean volume of Gadolinium-DTPA enhancing lesions was significantly higher during the pretreatment than the treatment period, and the enhancing lesion volume correlated with changes of hyperintense and hypointense lesion volumes only during the observation period. CONCLUSION: These data suggest that interferon-beta-1a has a stabilising effect on T1 weighted hypointense lesion volume.

Adult↗

Characterization of white matter damage in ischemic leukoaraiosis with diffusion tensor MRI.

BACKGROUND AND PURPOSE: Information on the neuropathological changes underlying ischemic leukoaraiosis is only available postmortem, and there are limited data on histological appearances early in the disease. Diffusion tensor imaging allows determination of the directionality of diffusion, which is greater in the direction of white matter bundles. Therefore, the technique might be expected to show loss of anisotropy (directional diffusion) in leukoaraiosis. METHODS: Nine patients with ischemic leukoaraiosis (radiological leukoaraiosis and clinical lacunar stroke) and 10 age-matched controls were studied. Diffusion tensor imaging was performed, and maps of diffusion trace and fractional anisotropy were constructed. Mean values of trace and fractional anisotropy were determined in standard regions of the anterior and posterior white matter in both hemispheres. RESULTS: In all patients with ischemic leukoaraiosis, a characteristic abnormal pattern was found, with loss of anisotropy and increased trace in the white matter. For example, in the right anterior white matter mean (SD) trace/3 was 1.12 (0.33) x10(-3) mm2 s-1 in patients and 0.75 (0.11) in controls (P=0.001). In the same region, fractional anisotropy was 0.53 (0.11) in patients and 0.78 (0.09) in controls (P<0.001). Within the white matter regions, there was a strong negative correlation between mean diffusivity and anisotropy (r=-0.92, P<0.0001). CONCLUSIONS: The characteristic pattern found on diffusion tensor imaging in this patient group is consistent with axonal loss and gliosis leading to impairment to and loss of directional diffusion. The "in vivo histological" information obtained may be useful in monitoring disease progression and in investigating the pathogenesis of the cognitive impairment that may be present.

Adult↗

Comparison of MS clinical phenotypes using conventional and magnetization transfer MRI.

OBJECTIVE: To identify differences in pathology between the principal clinical phenotypes of MS using conventional and magnetization transfer (MT) MRI. METHODS: T1-weighted and T2-weighted images as well as MT scans were obtained from 20 controls, 21 patients presenting with clinically isolated syndromes suggestive of MS, and 93 MS patients with relapsing-remitting, secondary progressive, benign, or primary progressive course. Metrics considered: hypointense T1 and T2 lesion volumes, average lesion MT ratio, average brain MT ratio, peak height and position from MT histograms. RESULTS: MS patients had lower MT metrics than controls. Patients with clinically isolated syndromes had MT measures similar to controls, whereas primary progressive MS patients had lower histogram peak height with normal peak position. Relapsing-remitting MS patients had lower MT measures, higher T2 lesion load and ratio of hypointense T1 to T2 lesion volumes than patients with clinically isolated syndromes, and lower MT ratio and peak height than benign MS patients. Benign MS patients were similar to controls and patients with clinically isolated syndromes. Secondary progressive MS patients had the lowest MT measures and highest lesion loads. CONCLUSIONS: Pathology in patients with clinically isolated syndromes is confined to modest tissue damage in the lesions seen on T2-weighted scans. Severe damage is important for the later development of disability. However, microscopic damage in normal-appearing white matter may be a major contributor to disability in primary progressive MS.

Adult↗

Echoplanar MRI in patients with an acute stroke syndrome.

An increasing number of patients with an acute stroke syndrome are being admitted to hospitals with on-site echoplanar MRI scanners. In this pictorial review, we describe our experience of an MRI protocol in the first 150 such patients scanned in our hospital. We illustrate some of the advantages of using echoplanar MRI. Diffusion and susceptibility weighted acquisitions may supplement conventional MR sequences by providing useful additional information about the age and location of the lesion, together with a high sensitivity to the presence of blood breakdown products.

Acute Disease↗