Osama Sabri

Correlation of positive symptoms exclusively to hyperperfusion or hypoperfusion of cerebral cortex in never-treated schizophrenics

BACKGROUND Studies of schizophrenia by single photon emission computed tomography (SPECT) and positron emission tomography (PET) have shown both regional cerebral hyperperfusion and hypoperfusion. The aim of this study was to examine the inter-relations between regional cerebral blood flow (rCBF), psychopathology, and effects of neuroleptic therapy. METHODS 24 never-treated patients with acute schizophrenia were examined with hexamethylpropyleneamine-oxime brain SPECT and assessed psychopathologically according to the positive and negative syndrome scale; they were studied again after neuroleptic treatment and psychopathological remission. rCBF values that deviated from those of 20 controls by more than 2 SD were regarded as abnormal. FINDINGS Both hyperperfused and hypoperfused patterns were found among schizophrenia patients during acute illness. The seven positive symptoms on the symptom scale showed different correlations with rCBF: formal thought disorders and grandiosity correlated positively (and strongly) with bifrontal and bitemporal rCBF; delusions, hallucinations, and distrust correlated negatively (and strongly) with cingulate, left thalamic, left frontal, and left temporal rCBF. Stereotyped ideas as a negative symptom correlated negatively (and strongly) with left frontal, cingulate, left temporal, and left parietal rCBF. After neuroleptic treatment (and reduction of positive symptoms), only negative symptoms correlated exclusively with bifrontal, bitemporal, cingulate, basal ganglia, and thalamic hypoperfusion. INTERPRETATION Different positive symptoms are accompanied by different rCBF values--some related to hyperperfusion, others to hypoperfusion. This finding may help to explain observed inconsistencies of perfusion patterns in drug-naïve schizophrenics.

Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG

The neurometabolic effects of the hallucinogen psilocybin (PSI; 0.2 mg/kg), the entactogen 3,4-methylenedioxyethylamphetamine (MDE; 2 mg/kg) and the stimulant d-methamphetamine (METH; 0.2–0.4 mg/kg) and the drugs’ interactions with a prefrontal activation task were investigated in a double-blind, placebo-controlled human [F-18]fluorodeoxyglucoseFDG-positron emission tomographicPET study (each group: n = 8). Subjects underwent two scans (control: word repetition; activation: word association) within 2–4 weeks. Psilocybin increased rMRGlu in distinct right hemispheric frontotemporal cortical regions, particularly in the anterior cingulate and decreased rMRGlu in the thalamus. Both MDE and METH induced cortical hypometabolism and cerebellar hypermetabolism. In the MDE group, cortical hypometabolism was more pronounced in frontal regions, with the exception of the right anterior cingulate, which tended to be hyperactive. Cognitive activation-related increases in left frontocortical regions were attenuated under all three psychoactive substances, but less so under MDE. Taking into account performance data and subjective reports on task difficulty, these effects may result from different mechanisms across the three groups. Our PSI data are in line with studies on acute schizophrenic patients suggesting frontal overactivity at rest, but diminished capacity to activate prefrontal regions upon cognitive demand. The MDE data support the hypothesis that entactogens constitute a distinct psychoactive substance class, which takes an intermediate position between stimulants and hallucinogens.

Benign versus malignant osseous lesions in the lumbar vertebrae : differentiation by means of bone SPET

Abstract.Bone scanning is a well-accepted and frequently performed diagnostic procedure with a high sensitivity, especially when single-photon emission tomography (SPET) acquisitions are added. However, the differentiation of benign from malignant osseous lesions often poses difficulty. The purpose of this study was to find out whether the particular localisation of an intraosseous lesion in a lumbar vertebra is an indicator of its aetiology. Bone scintigraphy including planar whole-body scans as well as SPET imaging of the lumbar spine was performed in 109 patients. The diagnoses of osseous lesions in the lumbar vertebrae were made strictly on the basis of the findings of magnetic resonance imaging, computed tomography or plain radiography. Sixteen patients had to be excluded from the study because they did not undergo adequate radiological examination. To determine the particular localisation of vertebral lesions in the bone scan, two experienced nuclear medicine physicians examined the studies independently while blinded to the radiological results. Four anatomical regions were differentiated within the vertebra: the vertebral body, the pedicle, the facet joints and the spinous process. Clopper-Pearson analysis, which takes into account the number of examinations, yielded the following probability intervals for the malignancy of intraosseous lesions in the lumbar spine: vertebral body 36.8%–57.3%, pedicle 87.7%– 100%, facet joints 0.8%–21.4% and spinous process 18.7%–81.3%. It was concluded that lesions affecting the pedicle are a strong indicator for malignancy, whereas involvement of the facet joints is usually related to benign disease. Lesions affecting the vertebral body or the spinous process do not show a clear tendency towards either malignancy or benignity. In contrast to other studies, a significant probability of malignancy (35.6%) was observed in lesions affecting exclusively the vertebral body.

Psychopathological and SPECT findings in never-treated schizophrenia

A total of 24 never‐treated (i.e. drug‐naive) actively psychotic schizophrenic patients, operationalized according to DSM‐III‐R, were examined in a pre‐post‐treatment design using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) and 99mTc‐HMPAO‐single photon emission computed tomography (SPECT) to assess regional cerebral blood flow (rCBF). The control subjects were 20 patients free of neurological and psychiatric symptoms. Before treatment there was only a slight hypofrontality, and hypoperfusion was observed in the left temporal superior region. After treatment, hypofrontality was reduced to one region and temporal hypoperfusion disappeared. Formal thought disorders were accompanied by increased rCBF in the bilateral frontal interior and left temporal superior regions. Delusions were associated with hypoperfusion in the anterior cingulate cortex. Negative symptoms showed no linkage to hypofrontality, either before or after treatment. Factor analysis showed delusions and hallucinations loading on different dimensions. The disorganized dimension correlated positively with all regions of interest, whereas these were negatively correlated with reality distortion.

Comparison of visual and ROI-based brain tumour grading using 18F-FDG PET: ROC analyses

Several studies have suggested that the use of simple visual interpretation criteria for the investigation of brain tumours by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) might be similarly or even more accurate than quantitative or semi-quantitative approaches. We investigated this hypothesis by comparing the accuracy of FDG-PET brain tumour grading using a proposed six-step visual grading scale (VGS; applied by three independent observers unaware of the clinical history and the results of histopathology) and three different region of interest (ROI) ratios (maximal tumour uptake compared with contralateral tissue [Tu/Tis], grey matter [Tu/GM] and white matter [Tu/WM]). The patient population comprised 47 patients suffering from 17 benign (7 gliomas of grade II, 10 non-gliomatous tumours) and 30 malignant (23 gliomas of grade III–IV, 7 non-gliomatous tumours) tumours. The VGS results were highly correlated with the different ROI ratios (R=0.91 for Tu/GM, R=0.82 for Tu/WM, and R=0.79 for Tu/Tis), and high inter-observer agreement was achieved (κ=0.63, 0.76 and 0.81 for the three observers). The mean ROI ratios and VGS readings of gliomatous and non-gliomatous lesions were not significantly different. For all measures, high-grade lesions showed significantly higher FDG uptake than low-grade lesions (P<0.005 to P<0.0001, depending on the measure used). Nominal logistic regressions and receiver operating characteristic (ROC) analyses were used to calculate cut-off values to differentiate low- from high-grade lesions. The predicted (by ROC) diagnostic sensitivity/specificity of the different tests (cut-off ratios shown in parentheses) were: Tu/GM: 0.87/0.85 (0.7), Tu/WM: 0.93/0.80 (1.3), Tu/Tis: 0.80/0.80 (0.8) and VGS: 0.84/0.95 (uptake < GM, but >> WM). The VGS yielded the highest Az (±SE) value (i.e. area under the ROC curve as a measure of predicted accuracy), 0.97±0.03, which showed a strong tendency towards being significantly greater than the Az of Tu/Tis (0.88±0.06; P=0.06). Tu/GM (0.92±0.04) and Tu/WM (0.91±0.05) reached intermediate Az values (not significantly different from any other value). We conclude that the VGS represents a measure at least as accurate as the Tu/GM and Tu/WM ratios. The Tu/Tis ratio is less valid owing to the high dependence on the location of the lesion. Depending on the investigators experience and the structure of the lesions, the easily used VGS might be the most favourable grading criterion.

Dual-head gamma camera 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography in oncological patients: effects of non-uniform attenuation correction on lesion detection

Abstract. The purpose of this study was to evaluate a dual head coincidence gamma camera (DH-PET) equipped with single-photon transmission for 2-[fluorine-18]-fluoro-2-deoxy-d-glucose (FDG) imaging in oncological patients. Forty-five patients with known or suspected malignancies, scheduled for a positron emission tomography (PET) scan, were first studied with a dedicated ring PET and subsequently with DH-PET. All patients underwent measured attenuation correction using germanium-68 rod sources for ring PET and caesium-137 sources for DH-PET. Ring PET emission scan was started 64±17 min after intravenous administration of 235±42 MBq FDG. DH-PET emission followed 160±32 min after i.v. FDG. Attenuation-corrected and non-attenuation-corrected images were reconstructed for ring PET and DH-PET. The image sets were evaluated independently by three observers blinded to clinical data and to results of conventional imaging. Attenuation-corrected ring PET as the standard of reference depicted 118 lesions, non-attenuation-corrected ring PET 113 (96%) lesions, and attenuation-corrected DH-PET and non-attenuation-corrected DH-PET, 101 (86%) and 84 (71%) lesions, respectively (P<0.05). The lesion detection rate of attenuation-corrected and non-attenuation-corrected DH-PET was almost similar for lesions >20 mm, whereas attenuation correction increased the detection rate from 60% to 80% for lesions ≤20 mm (P<0.01). A patient-based analysis revealed concordant results relative to attenuation-corrected ring PET for non-attenuation-corrected ring PET, attenuation-corrected DH-PET and non-attenuation-corrected DH-PET in 42 (93%), 36 (80%) and 31 (69%) patients, respectively. Differences might have influenced patient management in two (4%), six (13%) and ten (22%) patients, respectively. In conclusion, measured attenuation correction markedly improves the lesion detection capability of DH-PET. With measured attenuation correction the diagnostic performance of DH-PET is closer to that of dedicated ring PET.

Active and remitted schizophrenia: psychopathological and regional cerebral blood flow findings.

Single photon emission computed tomography with technetium-99m-d,l-hexamethylpropyleneamine oxime (99mTc-HMPAO) was used to assess regional cerebral blood flow (rCBF) during both florid and remitted stages of schizophrenia. Forty schizophrenic patients in an active phase of illness (diagnosis by DSM-III-R) were examined in two clinical states (ill vs. improved). At study entry, 24 patients were drug-naive, five were currently drug-free, and 11 were being treated with antipsychotic medication. Twenty medical patients who suffered from non-specific headaches but were free of neurological and psychiatric symptoms served as control subjects. At initial examination during the active phase of illness, cerebral perfusion patterns in the schizophrenic patients were characterized by both hypofrontality and hypotemporality. After remission, hypofrontality was no longer apparent in two of four frontal regions, and hypotemporality disappeared completely. As assessed with the Positive and Negative Syndrome Scale (PANSS), formal thought disorders, hallucinations, and ideas of grandiosity correlated with rCBF in the active phase of illness, but not after remission. In the remitted but not in the florid state, blunted affect, difficulties in abstract thinking, lack of spontaneity, and stereotyped thoughts correlated with rCBF. Correlations of five symptoms with rCBF changed significantly from first to second examination. The present study suggests that correlations between single psychotic symptoms and rCBF differ significantly in florid vs. remitted phases of schizophrenia.

”Ecstasy”-induced changes of cerebral glucose metabolism and their correlation to acute psychopathology

Abstract. The aim of this study was to determine the acute effects of the ”Ecstasy” analogue MDE (3,4-methylene dioxyethamphetamine) on cerebral glucose metabolism (rMRGlu) of healthy volunteers and to correlate neurometabolism with acute psychopathology. In a randomized double-blind trial, 15 healthy volunteers without a history of drug abuse were examined with fluorine-18-deoxyglucose (18FDG) positron emission tomography (PET) 110–120 min after oral administration of 2 mg/kg MDE (n=7) or placebo (n=8). Two minutes prior to radiotracer injection, constant cognitive stimulation was started and maintained for 32 min using a word repetition paradigm to ensure constant and comparable mental conditions during cerebral glucose uptake. Individual brain anatomy was represented using T1-weighted 3D flash magnetic resonance imaging (MRI), followed by manual regionalization into 108 regions of interest and PET/MRI overlay. After absolute quantification of rMRGlu and normalization to global metabolism, normalized rMRGlu under MDE was compared to placebo using the Mann-Whitney U-test. Acute psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) and rMRGlu was correlated to PANSS scores according to Spearman. MDE subjects showed significantly decreased rMRGlu in the bilateral frontal cortex: left frontal posterior (–7.1%, P<0.05) and right prefrontal superior (–4.6%, P<0.05). On the other hand, rMRGlu was significantly increased in the bilateral cerebellum (right: +10.1%, P<0.05; left: +7.6%, P<0.05) and in the right putamen (+6.2%, P<0.05). There were positive correlations between rMRGlu in the middle right cingulate and grandiosity (r=0.87, P<0.05), both the right amygdala (r=0.90, P<0.01) and the left posterior cingulate (r=0.90, P<0.01) to difficulties in abstract thinking, and the right frontal inferior (r=0.85, P<0.05), right anterior cingulate (r=0.93, P<0.01), and left anterior cingulate (r=0.85, P<0.05) to attentional deficits. A negative correlation was found between the left frontal operculum (Broca’s area) and attentional deficits (r=–0.85, P<0.05). The present study revealed acute neurometabolic changes under the ”Ecstasy” analogue MDE, indicating a frontostriatocerebellar imbalance paralleling other psychotropic substances or various psychiatric disorders.

Cerebral interregional correlations of associative language processing: a positron emission tomography activation study using fluorine-18 fluorodeoxyglucose.

Abstract. Even though there have been numerous positron emission tomography (PET) activation studies on the perfusional and metabolic bases of language processing, little is known about the intracerebral functional network of language and cognitive processes. It was the aim of this study to investigate the cerebral interregional correlations during voluntary word association versus word repetition in healthy subjects to gain insight into the functional connectivity of associative speech processing. Due to individual variability in functional anatomy, the study protocol was designed as an averaged single-subject study. Eight healthy volunteers performed a verbal association task during fluorine-18 fluorodeoxyglucose (18F-FDG) PET scanning. Two different tasks were performed in randomized order: (a) word repetition (after auditory presentation of nouns) as a control condition, and (b) word association (after auditory presentation of nouns) as a specific semantic activation. The regional metabolic rate of glucose (rMRGlu) was calculated after brain regionalization [112 regions of interest on individual 3D flash magnetic resonance imaging (MRI)] and PET/MRI realignment. Statistical analysis was performed for comparison of association and repetition and for calculation of interregional correlation coefficients during both tasks. Compared with word repetition, word association was associated with significant increases in rMRGlu in the left prefrontal cortex, the left frontal operculum (Broca’s area) and the left insula, indicating involvement of these areas in associative language processing. Decreased rMRGlu was found in the left posterior cingulum during word association. During word repetition, highly significant negative correlations were found between the left prefrontal cortex, the contralateral cortex areas and the ipsilateral posterior cingulum. These negative correlations were almost completely eliminated during the association task, suggesting a functional decoupling of the strict intercorrelation pattern.

Cerebral correlates of selective attention in schizophrenic patients with formal thought disorder: a controlled H2 15O-PET study

There is a widespread belief that formal thought disorders may be associated with disturbed selective attention in schizophrenia. Two hypotheses are derived: (1) patients with slightly pronounced formal thought disorders should differ from those with severely expressed formal thought disorders in terms of selective attention; and (2) the cerebral correlates of selective attention should be organised differently in mildly versus severely thought-disordered patients. We compared 20 female schizophrenic patients, one-half with mild, one-half with obvious formal thought disorders, and 10 control subjects on a neuropsychological battery and a cognitive activation task for selective attention (Go/NoGo) for the assessment of rCBF using H2 15O-PET. While the first hypothesis has not been confirmed, we found that the cerebral regions activated by selective attention in the two patient groups showed completely differing organisations. Low degrees of formal thought disorders were associated with significant activations in frontal superior gyrus and ventral anterior thalamic nucleus whereas high degrees of formal thought disorders were accompanied by significant activations in fusiform gyrus and precuneus. We suggest that differing task-solving strategies are applied by both clinical subgroups to achieve comparable results on the selective attention paradigm.