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Biomedical subjects

I D Wilkinson

Publications and source records attributed to I D Wilkinson.

At least 73 records · Page 4Linked to original sources

Cerebral proton magnetic resonance spectroscopy in asymptomatic HIV infection.

OBJECTIVE: To determine whether proton magnetic resonance spectroscopy (MRS) demonstrates central nervous system abnormalities in asymptomatic HIV-1-infected individuals. DESIGN: Both prospective and retrospective cross-sectional analyses of MRS in asymptomatic HIV-infected individuals. SETTING: Two specialists HIV/AIDS outpatient facilities in London. PARTICIPANTS: Eighty-four HIV-1 seropositive asymptomatic men; 29 HIV-1 antibody-negative homosexual men at high-risk for HIV infection and 48 HIV-1 antibody-negative men at low-risk for HIV infection as controls. MAIN OUTCOME MEASURES: Single voxel, gradient-localized proton MRS performed at 1.5 T with 135 msec echo-time and 1,600 msec repeat-time in an 8 ml volume of interest positioned in the parieto-occipital white matter. Spectroscopic results were expressed as ratios between the areas under the N-acetyl (NA), creatine (Cr) and choline (Cho) resonance peaks. RESULTS: There were no differences between those controls at high and those at low-risk for HIV infection. Comparing the combined control groups with the asymptomatic seropositive patients there were statistically significant differences in NA/Cho, NA/Cr (both P < 0.05) and NA/(NA + Cho + Cr) (P < 0.01). CONCLUSION: Abnormalities in cerebral biochemistry may be demonstrated by proton MRS during asymptomatic HIV-1 infection.

Brain↗

Measurement of synovial lining volume by magnetic resonance imaging of the knee in chronic synovitis.

OBJECTIVES: Current methods of monitoring chronic synovitis in a single joint rely on clinical examination derived indices, such as the detection of synovial thickening. This study aimed to develop a reproducible method for quantifying the volume of synovial lining in chronic synovitis using contrast enhanced magnetic resonance (MR) imaging. METHODS: The knees of 18 patients with chronic synovitis were examined (34 studies). A 2D T1 weighted FLASH sequence was used to evaluate the temporal enhancement of synovial structures after intravenous contrast. Synovial lining volume was calculated from subtraction of pre and post-enhancement 3D T1 weighted MP RAGE images with thresholding and pixel counting. Eleven patients were examined before and after intra-articular glucocorticoid (mean interval 14 weeks) and MR data compared with changes in clinical examination derived indices of disease activity. RESULTS: Synovial lining volume varied from 52-267 ml. The coefficient of variation in volume calculation was 3.5% for a single observer and was 3.8% for two observers. Synovial lining volume was quantified in all patients where synovial lining thickening could not be detected clinically. A decrease in synovial lining volume of > 40% was associated with an improvement in synovial lining thickening, detected clinically. Decreases in synovial lining volume were quantified by MR in two of three patients where changes in clinical examination derived indices were inconsistent. CONCLUSIONS: A reproducible method of estimating the volume of synovial lining in patients with chronic synovitis has been developed. MR measurement of synovial lining volume may quantify changes in chronic synovitis that remain unidentified by clinical measures.

Adult↗

Correlation of MRI and neuropathology in AIDS.

OBJECTIVE: To assess the correlation between findings on radiological and neuropathological examinations of the brain. METHODS: The formalin fixed brains of 19 patients who had died of AIDS were examined by MRI and neuropathology. RESULTS: The rate of identification of cerebral atrophy was similar radiologically and neuropathologically. However, only in half of these cases were the two examinations concordant in the diagnosis. Furthermore, in the 15 brains which had radiological diffuse white matter lesions, the underlying pathology was heterogeneous. CONCLUSIONS: The possible reasons for the inconsistencies, and their relevance to the interpretation of imaging studies, are discussed. The study suggests that the qualitative identification of atrophy in the postmortem brain is problematical and that diffuse white matter lesions seen on MRI are not indicative of a specific pathological process.

Acquired Immunodeficiency Syndrome↗

Proton MRS and quantitative MRI assessment of the short term neurological response to antiretroviral therapy in AIDS.

OBJECTIVE: To investigate MRI and proton spectroscopy changes in five patients with HIV associated dementia complex (HADC) treated with antiretroviral therapy. METHODS: Three markers were evaluated: (1) CSF/intracranial volume ratio; (2) T2 weighted signal ratio between parieto-occipital white and subcortical grey matter; and (3) metabolite ratios from long echo time (TE=135 ms) single voxel proton spectra of parieto-occipital white matter. RESULTS: Spectroscopic changes indicated initial increases in N-acetyl/(N-acetyl + choline + creatine) ratio (NA/(NA+ Cho+Cr)) and progression of atrophy after initiation of antiretroviral therapy in four of five patients. When the neurological status of the patients subsequently deteriorated (two of five patients), the NA/(NA+Cho+Cr) ratio also declined. CONCLUSIONS: Spectroscopic changes mirror reversible neuronal dysfunction. These objective, non-invasive techniques may be used for monitoring the neurological effects of antiretroviral drug therapy in patients with HADC.

AIDS Dementia Complex↗

Proton Spectroscopy in a Cross-Section of HIV-Positive Asymptomatic Patients Receiving Immediate Compared with Deferred Zidovudine (Concorde Study).

The purpose of this study was to examine by proton spectroscopy for any difference in cerebral metabolites in patients taking part in the Concorde study (comparing the efficacy of immediate versus deferred treatment with zidovudine on asymptomatic HIV infected individuals). Forty seven HIV positive male patients [29 immediate, 18 deferred zidovudine] were examined in the last 9 months of the therapeutic trial. Magnetic resonance imaging and proton spectroscopy were performed at 1.5 Tesla using a single voxel placed in the parieto-occipital white matter. No significant difference was found in metabolite ratios comparing immediate versus deferred zidovudine (NA/NA+Cho+Cr 0.52 vs. 0.52). High quality spectra were acquired in relatively large numbers of patients and logistically spectroscopy may be applied to clinical therapeutic studies.

HIV Infections↗

A multicenter proton magnetic resonance spectroscopy study of neurological complications of AIDS.

Human immunodeficiency virus (HIV) infection as seen in Europe and the United States has predominantly been contracted through male homosexual sex or intravenous drug abuse. In infected subjects, the brain is frequently affected both clinically and neuropathologically. The aim of this multicenter study has been to evaluate the value of single-voxel proton magnetic resonance spectroscopy (MRS) in the assessment of the neurological complications of acquired immunodeficiency syndrome (AIDS). MRS (voxel size = 8 ml, TR/TE = 1600/135 msec) was performed in 137 HIV-1-seropositive patients and 64 healthy controls without risk factors at three clinical MR sites operating at 1.5 T. The first result of this multicenter trial is that good reproducibility of results among participating sites was found. This demonstrates the reliability and robustness of MRS in the study of in vivo brain metabolism. In HIV patients, there was no significant correlation between metabolite ratios of brain detected by MRS and CDC grouping of patients or CD4 count. In contrast, the variations of brain metabolite ratios (NA/Cr, NA/Cho, and Cho/Cr) were related to the occurrence of encephalopathy, brain atrophy, or diffuse white matter lesions. There was no significant difference in brain metabolites between male homosexual AIDS patients and male intravenous drug user AIDS patients, whatever their neurological status (neurosymptomatic or neuroasymptomatic). Thus, the mode of transmission of HIV infection does not appear to affect the cerebral changes observed in the proton spectra from AIDS patients. Because of its ease of implementation and high information content, single-voxel proton MRS is likely to play a significant role in the evaluation of HIV-related encephalopathies.

Acquired Immunodeficiency Syndrome↗

Cerebral magnetic resonance relaxometry in HIV infection.

A prospective, cross-sectional study was designed to determine the magnetic resonance relaxation times of cerebral white matter in human immunodeficiency virus (HIV) infected individuals. T1 and T2 were estimated at 1.5 T using four-point methods. Seventy-five HIV-1 seropositive subjects, 48 seronegative blood donors, and 17 seronegative homosexual men were studied. Associations between relaxometry and clinical classification, neurological status, immunological status, and qualitative MRI were investigated. Statistically significant differences in white matter T1 relaxation time were found comparing low-risk control and AIDS groups (p < .005), seropositive subjects with neurological signs and those without (p < .005), and subjects with low (CD4 < or = 200 x 10(6)/l) and high (CD4 > 200 x 10(6)/1) CD4 cell counts (p < .05). These findings add to the body of information that reveals no HIV-related change in the brain before the onset of symptomatic immunosuppression and go someway to validating the previous visually rated, qualitative findings. Statistically significant difference in white matter T2 relaxation time were also found comparing the two control groups (p < .005) highlighting the need for appropriate controls.

AIDS Dementia Complex↗

The spectrum of MRI findings in CNS cryptococcosis in AIDS.

We retrospectively reviewed the cranial MRI appearances of 25 patients with AIDS and microbiologically proven central nervous system (CNS) cryptococcosis. Four patients had a normal scan. Ten patients had dilated perivascular Virchow-Robin spaces that were hyperintense on T2-weighted images. Nine of these patients developed progressive cryptococcomas, eight in the basal ganglia and one in the cerebral white matter. The cryptococcomas displayed high signal on T2-weighted and intermediate to low signal on T1-weighted images. None enhanced after dimeglumine gadopentetate. No abnormal dural or leptomeningeal enhancement was detected in any patient. One patient developed an acquired arachnoid cyst during treatment of CNS cryptococcosis which was thought to represent a focal collection of organisms and mucoid material within the subarachnoid space. In addition either cerebral atrophy and/or background white matter hyperintensity on T2-weighted images was present in 19/25 patients. In two patients the neuropathological findings at autopsy correlated well with the imaging abnormalities. In conclusion, this spectrum of MRI appearances in CNS cryptococcosis reflects the pathological mechanism of invasion by the fungus, but a normal scan or one with features of CNS HIV infection such as atrophy or white matter hyperintensity does not exclude the diagnosis.

AIDS-Related Opportunistic Infections↗

Sub-cortical white-grey matter contrast on MRI as a quantitative marker of diffuse HIV-related parenchymal abnormality.

White matter change occurs in human immunodeficiency virus (HIV) encephalopathy, which may be difficult to assess subjectively especially in the early stages of disease. This study applies a quantitative approach to the assessment of this finding. Sixty-three HIV seropositive subjects, 47 seronegative blood donors and 17 seronegative homosexual men underwent axial T2 weighted MRI of the brain at 1.5T. Quantitative analysis was performed by obtaining the pixel contrast between parieto-occipital white matter and head of caudate grey matter (Cwg). Highest values of Cwg were found in a subgroup of subjects with AIDS who had diffuse/patchy white matter abnormalities and atrophy on qualitative image assessment. Statistically significant differences were found in Cwg between subjects with high (> or = 200 x 10(6)/I) and low (< 200 x 10(6)/I) CD4 lymphocyte counts (P < 0.05) and between subjects with and without HIV-1 associated cognitive/motor complex (P < 0.05). This technique provides an objective measure of diffuse HIV-related parenchymal abnormality seen on T2 weighted MRI.

AIDS Dementia Complex↗

Blood-Brain Barrier Integrity in HIV Infection:Evaluation by Contrast-Enhanced Magnetic Resonance Imaging.

This study assesses the integrity of the blood-brain barrier (BBB) in human immunodeficiency virus (HIV) seropositive individuals to magnetic resonance imaging (MRI) contrast agent Gd-DTPA. Twelve HIV seropositive patients and six control subjects had T2-weighted and serial pre- and post-contrast TI-weighted MRI. Ten of the twelve seropositive patients demonstrated white matter hyperintensity with or without atrophy on T2-weighted MRI and 8/10 who underwent neurological examination demonstrated neurological abnormalities. No statistically significant differences of trends in white matter pixel values were observed between pre- and post-contrast scans in any of the patients or controls. Serial T1-weighted MRI does not demonstrate any change in the integrity of the BBB to Gd-DTPA in HIV seropositive patients, regardless of the presence or absence of white matter hyperintensity with or without atrophy on T2-weighted MRI or clinical signs of HIV-I associated with cognitive/motor complex.

Blood-Brain Barrier↗

Cranial MR imaging in Wilson's disease.

OBJECTIVE: The purpose of the study was to describe the range of abnormalities seen on cranial MR images of patients with Wilson's disease and correlate the findings with clinical severity, duration of disease, and duration of neurologic signs and symptoms before treatment. In those patients with serial studies, the changes on MR images were compared with the clinical response. SUBJECTS AND METHODS: Twenty-five patients with Wilson's disease underwent MR imaging of the brain using conventional spin-echo sequences (n = 25), phase maps (n = 8), and partially refocused interleaved multiple-echo sequences (n = 5). RESULTS: MR imaging findings were abnormal in 22 patients and normal in three patients. The basal ganglia were interpreted as abnormal in 19 (86%) of 22 patients, involving the putamen in 19 (86%), the thalami in 12 (54%), the caudate head in 10 (45%), and the globus pallidus in nine (41%). We found a predilection for involvement of the outer rim of the putamen and the ventral nuclear mass of the thalami. The claustrum was abnormal in three patients. The midbrain was abnormal in 17 (77%) of these 22 patients, affecting predominantly the tegmentum but also the substantia nigra, red nuclei, inferior tectum, and crura. The pons was abnormal in 18 (82%) of 22 patients, and the cerebellum was abnormal in 11 patients (50%), with involvement of the superior and middle cerebellar peduncles. Atrophy was present in 18 (82%) of 22 patients, and cortical white matter changes were apparent in 13 (59%) of 22 patients. The scan of one untreated patient revealed shortening of the T1 relaxation time in the thalami, which was consistent with the paramagnetic effects of copper. Phase maps and partially refocused interleaved multiple-echo sequences performed in eight and five patients, respectively, and used to reveal a susceptibility change induced by iron or copper showed normal findings. We found a significant inverse relationship between severity, but not extent, of change in signal intensity and the length of untreated disease (p = .030) and the total duration of disease (p = .015). The study group was too small to show a correlation with clinical findings. Changes seen on MR images matched the clinical response to treatment in only two of the seven patients who underwent follow-up studies. CONCLUSION: MR imaging revealed abnormalities in the basal ganglia, cerebral white matter, midbrain, pons, and cerebellum. The paramagnetic effects of copper were detected only in untreated patients. Patients with a longer duration of disease had less severe changes in signal intensity. MR imaging was of limited value in follow-up.

Adolescent↗

Spatial data analysis in the quantitative assessment of cerebral white matter pathology on MRI in HIV infection.

This study was carried out using MRI (proton density--and T2-weighted) on 16 HIV-negative controls, 9 symptom-free HIV-positive patients and 25 with CDC IV HIV disease. The studies from this last group had previously been allocated by a radiologist to the following categories: 8 with focal mass lesions and normal-appearing white matter; 9 with diffuse encephalopathy (high signal on T2-weighted images, affecting most or all of the white matter) and 8 with patchy encephalopathy (high signal affecting only one or two areas within the white matter). Moran's I, a statistic of spatial autocorrelation, was calculated for the grey-scale values of a sampled pixel array from a central white matter region of each of the images. All values of Moran's I calculated in this study showed a large positive excess over the expected value under randomisation, indicating highly significant positive auto-correlation in the spatial arrangement of the grey-scale values. On T2-weighted images a statistically significant increase in the mean value of Moran's I, compared with controls, was found in the diffuse encephalopathy group, indicating that quantifiable changes in the spatial autocorrelation of pixel data can be related to recognised qualitative changes in the appearance of white matter in subjects with HIV disease. A lesser, but significant, rise in the mean value of Moran's I was also found in the focal mass lesion group, suggesting that changes in spatial autocorrelation may indicate pathological change in advance of qualitative MRI changes.

AIDS Dementia Complex↗

Short echo time proton spectroscopy of the brain in HIV infection/AIDS.

Short echo time proton spectra have been acquired from the brains of 30 male homosexual Acquired Immunodeficiency Syndrome (AIDS) patients and 12 age-matched control subjects on a 1.5 T MR system. The acquisition protocol used stimulated acquisition voxel localisation with a voxel size of 8 ml and repeat, echo, and mixing times of 5000, 20, and 30 ms, respectively. A single 25.6-ms Gaussian water suppression pulse was used with 128 spectral acquisitions and the data were eddy current corrected using a water reference. Baseline-corrected spectra were nonlinearly least squares fitted to a model function consisting of Gaussian functions representing the major metabolites reported in short echo proton spectra. Results indicate that the N-acetyl/creatine (NA/Cr) ratio is significantly reduced by 20% in AIDS patients [NA/Cr = 1.91 (0.51)] compared to control subjects [NA/Cr = 2.37 (0.25)] at short echo times.

AIDS Dementia Complex↗

Toxoplasmosis and primary central nervous system lymphoma in HIV infection: diagnosis with MR spectroscopy.

PURPOSE: To differentiate intracranial lymphoma from Toxoplasma gondii lesions in patients infected with the human immunodeficiency virus, by means of localized spin-echo proton magnetic resonance (MR) spectroscopy. MATERIALS AND METHODS: Twenty-seven lesions were studied (18 T gondii lesions, nine lymphoma lesions) at 1.5 T. Spectra were acquired at an echo time of 135 msec from voxels centered on the lesions. Both visual analysis and spectral fitting were used to obtain metabolite ratios for choline (Cho), creatine (Cr), N-acetyl (NA), lactate, and lipids. RESULTS: Three spectral categories were seen. One had large lipid peaks with suppression of other metabolites. Another had an elevated Cho/Cr ratio with relatively diminished NA. The third had features of the other two. Examples of each spectrum type were acquired from both T gondii and lymphoma lesions. Neither method of analysis allowed differentiation between lesion types. MR spectroscopy showed an overlap of spectra. CONCLUSION: The authors conclude that toxoplasmosis and lymphoma cannot be differentiated with spin-echo proton MR spectroscopy at 135 msec.

AIDS-Related Opportunistic Infections↗

Proton spectroscopy in HIV infection: relaxation times of cerebral metabolites.

In vivo proton spectroscopy has demonstrated abnormalities in the cerebral metabolite ratios from subjects with acquired immunodeficiency syndrome (AIDS). Some of the sequences employed are subject to T1 or T2 weighting, which may affect spectroscopic interpretation. The relaxation times of choline (Cho), creatine (Cr), and N-acetyl (NA) resonances have been estimated at 1.5 T in 21 patients infected with the human immunodeficiency virus (HIV) and 8 controls using gradient localised, spin-echo spectroscopic sequences of varying echo and repetition times. A statistically significant increase in the T2 of NA was found in the HIV seropositive patients who had diffuse abnormalities on MR imaging consistent with HIV encephalopathy (493 +/- 199 ms) when compared to controls (292 +/- 118 ms; p < .05). No other statistically significant differences were found in the relaxation times between patients and control subjects. These results demonstrate that signals from the NA resonance obtained using long echo time sequences in subjects who are HIV seropositive are not solely indicative of metabolite concentration.

Adult↗

Cerebrospinal fluid-intracranial volume ratio measurements in patients with HIV infection: CLASS image analysis technique.

PURPOSE: To prospectively study the cerebrospinal fluid volume-total intracranial volume ratio (CSF/ICV) in human immunodeficiency virus (HIV)-infected patients at various stages of disease. MATERIALS AND METHODS: A total of 258 volume measurements were obtained with use of a 1.5-T magnetic resonance (MR) imager and the cluster localized automated spherical segmentation technique (which reduces two-dimensional pixel data from dual spin-echo MR images to a one-dimensional histogram) in 69 control subjects and 189 HIV-infected patients. RESULTS: The CSF/ICV was statistically significantly increased in patients with late-stage (Centers for Disease Control and Prevention group IV) acquired immunodeficiency syndrome (AIDS) (0.16 +/- 0.05 [standard deviation]) compared with seronegative control subjects (0.12 +/- 0.03) and patients without symptoms (0.13 +/- 0.03). CONCLUSION: No substantial change in CSF/ICV occurs until development of late-stage AIDS.

Acquired Immunodeficiency Syndrome↗

Localized cerebral proton MR spectroscopy in HIV infection and AIDS.

PURPOSE: To document differences in the cerebral proton MR spectra of patients with early and late stages of human immunodeficiency virus (HIV) infection. METHOD: We studied the relative N-acetyl-aspartate (NAA) levels by localized proton spectroscopy of the parietooccipital region of the brain in 43 HIV-seropositive patients, including 26 with an acquired immunodeficiency syndrome (AIDS)-defining diagnosis, and in eight control subjects. RESULTS: Reduced relative NAA levels were shown in those HIV-1-seropositive patients: 1) with AIDS against HIV-1-seropositive patients without AIDS (P < .04); 2) with HIV-1-associated cognitive/motor complex against neurologically healthy patients (P < .007); 3) with encephalopathic changes on MR against those with normal imaging (P < .001); and 4) on follow-up against their results on initial study (P < .03). CONCLUSIONS: By clinical (Centers for Disease Control classification) and radiologic (MR evidence of white-matter disease) criteria indicating late-stage HIV infection, reduced relative levels of NAA have been demonstrated. Spectroscopic abnormalities can be quantitatively tracked with time. This paper demonstrates the clinical use of detecting NAA as a putative in vivo measure of the neuronal loss that has been demonstrated in postmortem studies of patients with AIDS. This neuronal loss, which is believed to underlie the HIV-1-associated cognitive/motor complex, is thought to be attributable directly or indirectly to the presence of HIV in the brain. Proton spectroscopy may serve as a quantitative noninvasive indicator of this aspect of cerebral involvement in HIV disease.

AIDS Dementia Complex↗