Marc Steinling

A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging

Differences in grading signal hyperintensities on magnetic resonance imaging may explain earlier reported conflicting results in studies of normal aging and dementia. We designed a new rating scale in which periventricular and white matter signal hyperintensities as well as basal ganglia and infratentorial signal hyperintensities are rated separately in a semiquantative way. In this study we compared the inter- and intra-observer agreements of this scale to the widely used rating scale of Fazekas. We confirmed the poor to reasonable intra- and inter-observer agreements of the Fazekas scale. The new scale, although more elaborate, provided good agreements with respect to the white matter, basal ganglia and infratentorial signal hyperintensities. In rating periventricular hyperintensities this scale yielded no advantage. It is concluded that this scale may be of use in studies especially focussing on deep white matter pathology on MRI, because it provides more detailed information, with good intra- and inter-observer reliability.

Fetal cortical activation to sound at 33 weeks of gestation: a functional MRI study.

Hearing already functions before birth, but little is known about the neural basis of fetal life experiences. Recent imaging studies have validated the use of functional magnetic resonance imaging (fMRI) in pregnant women at 38-weeks of gestation. The aim of the present study was to examine fetal brain activation to sound, using fMRI at the beginning of the third trimester of pregnancy. 6 pregnant women between 28- and 34-weeks of gestation were scanned using a magnetic strength of 1.5 T, with an auditory stimulus applied to their abdomen. 3 fetuses with a gestational age of 33 weeks, showed significant activation to sound in the left temporal lobe, measured using a new data-driven approach (Independent Component Analysis for fMRI time series). Only 2 of these fetuses showed left temporal activation, when the standard voxel-wise analysis method was used (p=0.007; p=0.001). Moreover, motion parameters added as predictors of the General Linear Model confirmed that motion cannot account for the signal variance in the fetal temporal cortex (p=0.01). Comparison between the statistical maps obtained from MRI scans of the fetuses with those obtained from adults, made it possible to confirm our hypothesis, that there is brain activation in the primary auditory cortex in response to sound. Measurement of the fetal hemodynamic response revealed an average fMRI signal change of +3.5%. This study shows that it is possible to use fMRI to detect early fetal brain function, but also confirms that sound processing occurs beyond the reflexive sub-cortical level, at the beginning of the third trimester of pregnancy.

Cognitive and SPECT characteristics predict progression of Parkinson's disease in newly diagnosed patients.

ObjectiveTo identify features in cognitive functioning and regional cerebral blood flow (rCBF) in newly diagnosed Parkinson’s disease (PD) patients and to determine whether these factors are able to predict the progression of the disease in general and the development of cognitive decline in particular.Methods50 previously treatment-naive PD patients participated in the study. Cognitive assessment and SPECT were performed twice: at the time of diagnosis and then 3 years later. Six patients died or refused to continue. The Mattis dementia rating scale, the WAIS-R digit span test, a word list learning/recall test, a word fluency task and the Stroop word-colour test were used to assess cognitive function. rCBF was measured in 10 pairs of regions of interest. Principal component analysis of the data from the final examination was used to determine which variables allowed the formation of patient subgroups. Thereafter, factorial discriminant analysis (FDA) was performed in order to obtain a predictive model of these final classes.ResultsA stepwise procedure enabled the identification of 3 clusters (26, 16 and 2 patients).As the patients in the smallest cluster met the criteria for dementia at the final examination, they were discarded from further analyses. All the cognitive variables contributed to the constitution of the two other clusters. Age, educational level and all the rCBF parameters also contributed but to a lesser extent. Comparison of these groups showed reduced overall cognitive efficiency and an exacerbated subcorticofrontal syndrome in the 16-patient cluster. FDA showed that the best predictive model for the final classes was based on 7 variables: educational level, semantic and alternating word fluency, Stroop interference index and the right medial frontal, left parietal and left lenticular nucleus rCBF findings.ConclusionEven though both cognitive and rCBF parameters help predict the progression of newly diagnosed PD patients and bearing in mind the limitations of the SPECT method used here, it appears that the contribution of cognitive assessment is greater than that of rCBF measurement.

SPECT imaging, clinical features, and cognition before and after low doses of amisulpride in schizophrenic patients with the deficit syndrome

The aim of the study was to examine the action of low-dose amisulpride (100 mg/d), an atypical antipsychotic from the benzamide class with a high affinity for the D2 and D3 dopamine receptors, given for 4 weeks in 19 schizophrenic patients with the deficit syndrome, in terms of clinical response, modifications in their cognitive performance and changes in brain perfusion values. A secondary objective was to distinguish between primary and secondary deficit, according to Carpenters definition. Both efficacy and a relatively low rate of side effects of low-dose amisulpride in the deficit forms of schizophrenia were found as expected from earlier placebo-controlled studies. Our study found significant changes in the cerebral blood flow, before and after treatment, more marked in the frontal area and particularly in the dorso-lateral frontal area. A significant improvement of cognitive function was found after treatment, without a link to any particular changes in a loco-regional perfusion value. Finally, a distinction between primary and secondary deficit showed a higher percentage of clinical improvement in the patients with a secondary deficit. The psychometric and cerebral perfusion changes were no different in the two groups.

Evidence for Atrophy of the Corpus callosum in Alzheimer’s Disease

Patients with late-onset Alzheimers disease (AD) have more white matter changes on magnetic resonance imaging (MRI) than controls. To test the hypothesis that AD patients might have also atrophy of the corpus callosum (CC), we compared the CC thickness on MRI from 20 AD patients and 21 controls. We found a significant reduction in the CC thickness in AD compared with age-matched controls (p < 0.01). We demonstrated that atrophy of the CC depends mainly on the diagnosis of senile dementia of the Alzheimer type and at a lower degree on the diagnosis of presenile AD but neither on age nor on ventricle enlargement. This result suggests that beside the greater severity of white matter involvement in late-onset AD, atrophy of the CC may also be present.

The Use of SPECT in a Multidisciplinary Memory Clinic

We tested the interobserver reliability of visual rating of HMPAO-SPECT imaging in 271 outpatients referred to a memory clinic, and followed over 1 year. The clinical diagnoses were Alzheimers disease (n = 156), frontotemporal dementia (n = 47); vascular dementia (n = 21), senile dementia of Lewy body type (n = 12), anxiety/depressive disorders (n = 14) and miscellaneous memory disorders (n = 21). The interobserver agreement was good (k = 0.68). However, the heterogeneity of the patterns-independent from demographic data, age at onset and duration of the disease- and their lack of sensibility and specificity limited the contribution of SPECT for diagnostic purposes in routine practice.

Tomographic measurements of regional cerebral blood flow in progressive supranuclear palsy and Parkinson's disease

Intellectual changes observed in progressive supranuclear palsy (PSP) are sometimes seen with lesser intensity in Parkinsons disease (PD). Cognitive impairment of PSP has been attributed to a frontal lobe dysfunction explaining the frontal cortex hypometabolism detected by PET. To establish whether this frontal hypometabolism is more pronounced in PSP than in PD, we compared frontal and temporo‐parietal cerebral blood flow (CBF) indexes studied by SPECT using Tc99m HmPAO in 18 PSP, 18 PD and 8 control subjects. For each patient neuropsychological performances were also assessed. A significant left frontal hypoperfusion was observed in PSP (mean index value: 0.78 ± 0.03, p < 0.01) and PD (0.78 ± 0.04, p < 0.05) as compared to controls (0.84 ± 0.03), whereas there was no difference between PSP and PD. No correlation was discovered between neuropsychological performances and frontal cortical index changes. This frontal uptake reduction of Tc99m HmPAO in PSP and PD could result from a disconnection phenomenon secondary to subcortical lesions. In both groups mean frontal indexes showed only a left frontal hypoperfusion suggesting that subcortical structures might be asymmetrically involved in early stages of the diseases. The lack of difference for indexe values between PSP and PD might be explained by the difference between the mean disease duration: 4.3 years for the PSP and 7.8 years for the PD. It might also suggest that frontal CBF reduction exists in the same proportions in PD and PSP, but at a later stage in the former case.

Is There a Typical Pattern of Brain SPECT Imaging in Alzheimer’s Disease?

The identification of new nosological forms such as Lewy body disease (LBD) requires a re-evaluation of the patterns observed in brain functional imaging in the various forms of dementia. We studied 60 demented patients, divided into three groups and fulfilling the clinical criteria for Alzheimer’s disease (AD), LBD and frontotemporal dementia (FTD), using Tc-HMPAO and a brain-dedicated SPECT system. After normalisation we applied a cut-off at two levels according to previously established criteria. We reaffirmed the already established data concerning FTD (mainly a bilateral frontal decrease) and for LBD (a severe diffuse decrease in the frontal regions and also in the posterior association cortex). In contrast, the decrease in AD was strictly limited to the parieto-occipital cortex, irrespective of the severity of the cognitive decline. We hypothesise that the major simplification concerning the pattern observed in AD can be explained by the fact that patients suffering from LBD have previously been included in the groups of AD patients.

Pulmonary perfusion scintigraphy: a tool to detect the presence of pulmonary artery involvement in Takayasu's arteritis.

OBJECTIVE Takayasu arteritis (TA) is a large-vessel vasculitis that can also involve pulmonary arteries. The aim of this study was to evaluate the frequency of pulmonary artery involvement in TA patients using pulmonary perfusion scintigraphy (PPS) and to determine the characteristics of patients with pulmonary artery involvement. METHODS Twenty-one patients classified as having TA underwent PPS. PPS positivity was defined as the presence of perfusion defects with normal ventilation. TA diagnosis was assessed using American College of Rheumatology (ACR) and/or Ishikawas modified criteria. RESULTS Twenty-one patients (median age 36 years [range; 21-78]; 18 females) were analyzed. PPS was positive in 12 (57%) patients. Pulmonary symptoms were present in 4/12 patients with positive PPS, but none in patients with negative PPS. Among the 12 patients with positive PPS, eight patients (67%) were asymptomatic with regard to pulmonary involvement. No difference was noted between patients with positive and negative PPS with respect to general characteristics, vascular involvement, biological parameters or treatment regimen. PPS sensitivity was 100%, specificity at 53% and predictive negative value at 100% in patients with TA relative to the presence of pulmonary symptoms. CONCLUSION Although frequent, pulmonary artery involvement in TA is often asymptomatic. Its systematic detection by PPS could be valuable in the diagnosis of TA.

99mTc-MIBI brain SPECT as an indicator of the chemotherapy response of recurrent, primary brain tumors.

BackgroundMalignant brain tumors carry a pejorative prognosis and necessitate aggressive therapy. Chemotherapy can be used in cases of tumor recurrence. With limited response rate and potential toxicity to chemotherapeutic treatment in patients with recurrent glioma, reliable response assessment is essential. AimTo define the place of 99mTc hexakis 2-methoxyisobutylisonitrile (99mTc-MIBI) Single Positron Emission Computed Tomography (SPECT) in monitoring chemotherapy response in recurrent primary brain tumors. MethodsIn a retrospective analysis, thirty patients were investigated with MIBI SPECT. Imaging was performed 1h after the intravenous injection of 555 MBq of 99mTc-MIBI using a dedicated SPECT system. A MIBI uptake index (UI) was computed as the ratio of counts in the lesion to those in contralateral region. For all patients, we compared changes over time in UI with MRI and clinical data. ResultsThe changes in UI agreed well with the clinical and MRI-based assessments in 97% of cases. In 44% of these cases, the scintigraphic response appeared before the MRI response. In instances of treatment failure or rebound, the concordance between scintigraphy and MRI was 52%, and the scintigraphic response appeared before the MRI response in 48% of cases. ConclusionThis study confirms our previous results obtained on a short series of patients with recurrent glioma, concerning the usefulness of MIBI SPECT in prediction of chemotherapy response. Moreover, in cases of tumor progression, we show that MIBI SPECT is an earlier indicator of escape from chemotherapy, an average 4 months before MRI changes.