M. A. Hall-Craggs

Evidence of CNS impairment in HIV infection: clinical, neuropsychological, EEG, and MRI/MRS study

OBJECTIVES To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (<350), and seropositive asymptomatic subjects, both groups being followed up in a longitudinal study. Control groups consisted of seronegative subjects from the same genitourinary medicine clinics. RESULTS This report sets out the cross sectional findings at the seventh visit in the longitudinal study. Patients with AIDS had more signs of neurological dysfunction, poorer performance on a neuropsychological test battery, were more likely to have an abnormal EEG, and to have abnormalities on MRI. They more often had cerebral atrophy, abnormal appearing white matter, , and abnormal relaxometry and spectroscopy. There was little evidence of abnormality in seropositive people who had a CD4 count >350 compared with seronegative people from a similar background. CONCLUSIONS Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychogical assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.

Comparison of magnetic resonance imaging with neuropathological findings in the diagnosis of HIV and CMV associated CNS disease in AIDS.

OBJECTIVES: To compare the results of clinical assessment and MRI with neuropathological findings in the diagnosis of HIV and cytomegalovirus (CMV) associated CNS disease. METHODS: A retrospective study of 35 patients infected with HIV who were examined at necropsy between four and 70 (median 20) days after neurological assessment and MRI. RESULTS: Of the 35 patients, 19 had diffuse white matter hyperintensity on T2 weighted MRI, six of whom also had focal lesions. Nine other patients had focal white matter lesions and seven had changes in cortical atrophy only. Necropsy in the 19 with diffuse white matter hyperintensity showed HIV leukoencephalopathy (HIVLEP) with encephalitis in 10, CMV encephalitis in three, both HIVLEP/HIV encephalitis and CMV encephalitis in one, lymphoma in three, and non-specific inflammation in two. Necropsy in the 16 other patients without diffuse white matter hyperintensity showed CMV encephalitis in six, HIV encephalitis (without HIVLEP) in two, CMV encephalitis and HIVLEP/HIV encephalitis in one, non-HIV associated abnormalities in five, herpes simplex encephalitis in one, and lymphoma in one. CMV DNA was detected in CSF of five of seven patients with CMV encephalitis and in two of two with CMV associated polyradiculopathy but without CMV encephalitis. Diffuse white matter hyperintensity on MRI had a sensitivity of 100%, a specificity of 66.6%, and a positive predictive value of 58% for diagnosis of HIVLEP. CONCLUSION: Diffuse white matter hyperintensity on MRI can be due to either HIV or CMV associated pathology or non-specific abnormalities.

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.

The assessment of postmortem brain volume; a comparison of stereological and planimetric methodologies

Abstract We compared two methods of estimating the volume of 10 formalin-fixed brains using MRI. MRI was performed and total brain volume was then assessed using two distinct techniques: a stereological point-counting technique based on the Cavalieri principle, and an edge-tracing technique. The total brain volumes obtained using these two techniques were similar and correlated closely with each other (r = 0.97). Both methods could be optimised to a similar degree while maintaining the coefficient of error at an acceptably low level. However, the stereological assessment of brain volume required between 20 min and 30 min per brain, depending on the number of points per sampling grid, compared with 1 h per brain using the planimetric method. Thus, while planimetric and stereological approaches yield very similar results, the stereological method has the advantage of greater speed and, therefore, efficiency.

Cerebral volumes and spectroscopic proton metabolites on MR: Is sex important?

One of the factors that may influence the selection of appropriate controls for MR studies of the brain is gender. This study compared calculated intracranial volumes and proton spectroscopic metabolite ratios obtained from male and female volunteers. Thirty-two males (mean age = 36; range = 30-53 yr) and 19 females (mean age = 39; range = 26-53 yr) underwent investigation at 1.5T. Brain, cerebrospinal fluid (CSF), and intracranial (ICV = brain + CSF) volumes were measured by the CLASS technique on data acquired using an axial dual spin-echo imaging sequence (TE = 20/90 ms, TR = 3500 ms). Proton spectra (TE = 135 ms, TR = 1600 ms) were acquired from an 8 ml cubic region placed in parieto-occipital white matter. The mean male and female brain, CSF and ICV were significantly different (p < .005). However, the mean CSF/ICV ratios of the two groups were not significantly different. The N-acetyl/choline and choline/creatine metabolite ratios of the two groups were significantly different (p < .05). When comparing proton metabolite ratios and absolute brain volumes between groups, gender is an important factor. CSF/ ICV ratios do not appear to depend on gender.

Magnetic resonance imaging control of laser destruction of hepatic metastases: correlation with post-operative dynamic helical CT

SummaryInterstitial laser photocoagulation (ILP) is currently limited by deficient per-procedural monitoring. The purpose of this study was to evaluate MR control of ILP of hepatic metastases. Twenty-two laser activations were used to treat eight metastases in seven patients under local anaesthesia and sedation. Laser energy was delivered via optical fibres positioned in the tumour under ultrasound guidance. T1-weighted FLASH and spin-echo sequences were used to monitor the procedure. Enhanced CT was performed at 24 h to assess thermal necrosis. FLASH imaging showed an enlarging area of signal change during ILP. The final extent of this correlated closely with the extent of tissue necrosis on CT. Spin-echo imaging was disappointing because of poor contrast between the treated tissue and normal liver/untreated tumour. Per-procedural MR imaging accurately and reliably depicts ILP-induced necrosis. MR control may permit more widespread application of ILP to the treatment of hepatic tumours.

The prevalence of paranasal sinus disease in HIV infection and AIDS on cranial MR imaging.

Sinusitis poses a difficult clinical challenge in the management of patients with AIDS because of high rates of relapse and the association with unusual pathogens. To determine the prevalence and severity of sinus disease in this group we prospectively analysed the condition of the paranasal sinuses shown on cranial MR scans of 156 patients referred for the investigation of suspected intracranial pathologies. These included 104 HIV seropositive patients, including 93 with an AIDS-defining diagnosis (CDC IV). Forty-two scans were performed on age-matched controls. The scans were timed to control for seasonal variations in sinus disease and were interpreted by two radiologists who were blinded to the clinical and serological status of the patients. Severe mucosal disease (more than one sinus showing > 75% obliteration) or moderate mucosal disease (only one sinus showing > 75% obliteration) was seen in 15.1% (14/93) patients with AIDS and none of the 42 controls (chi 2 = 6.73, P < 0.01). The mean maximum mucosal thickness in patients with AIDS was significantly greater than the control group (P < 0.001) and also significantly greater than in seropositive patients who had not had an AIDS-defining diagnosis (CDC II/III) (P = 0.006). Paranasal sinus mucosal abnormalities seen on MRI are greater in prevalence and severity in patients with AIDS and about one in seven would be expected to have at least one sinus largely obliterated.

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.

Magnetic resonance imaging of interstitial laser photocoagulation of normal rat liver: imaging-histopathological correlation

SummaryAim - To correlate the magnetic resonance imaging signal changes observed during interstitial laser photocoagulation (ILP) therapy with histopatho-logical analysis of tissue necrosis. A 1.5T MR system was used. Lesions were produced with a diode laser (805 nm) in the liver of normal Wistar rats at laparotomy under general anaesthesia and imaged during treatment. Seventeen lesions were monitored with a T1-weighted spin echo (T1WSE) sequence, and 15 with a FLASH sequence. Treated tissue was removed and stained for NADPH-diaphorase to determine the extent of devitalization. Per-procedural T1WSE showed an expanding area of low signal which developed a high signal rim as ILP progressed. FLASH imaging showed an expanding area of low intensity which was replaced by a complex region of signal change as treatment progressed. Good imaging-histopathological correlation was shown: for T1WSE, r2=0.88 (P < 0.001) and for FLASH, r2=0.95 (P < 0.001). MR imaging during hepatic ILP accurately shows the extent of tis...

High magnetic susceptibility coatings for visualisation of optical fibres on a specialised interventional MRI system

Abstract The aim of this study was to develop methods of visualising optical fibres on MRI scans for monitoring interstitial laser therapy. Scans were performed on a specialised MRI extremity scanner at 0.17 T. Optical fibres of 0.4 mm diameter used for delivering laser energy were coated with iron particles from a superferromagnetic contrast agent. MR images of the fibres were acquired using gradient echo sequences (TR/TE = 300/10, 1 mm in-plane, 3 mm slice) and assessed for fibre visibility. Coated fibres could be resolved as lines 2 ± 1 mm wide using the gradient echo sequence. Uncoated fibres were invisible on the sequences used for in vivo therapy monitoring due to partial volume averaging. It is concluded that optical fibre visualisation by MRI may be improved by coating with ferromagnetic particles. Biocompatibility requires further assessment, but direct coating appears to be a promising method for fibre visualisation in MR-guided laser therapy.