Psychotic symptoms in major depressive disorder are associated with reduced regional cerebral blood flow in the subgenual anterior cingulate cortex: a voxel-based single photon emission computed tomography (SPECT) study

BACKGROUND: Delusions and/or hallucinations are not an uncommon feature in severe major depressive episodes. Functional imaging studies of depression have been widely reported in the literature, but few of these have attempted to investigate the neurophysiological correlates of psychotic symptoms. METHODS: We measured resting regional cerebral blood flow (rCBF) with the (99m)Tc-ECD SPECT technique in patients with major depressive disorder with (n=9) and without (n=12) psychotic features, as well as in a group of healthy volunteers (n=12). Between-group rCBF comparisons were performed using the voxel-based statistical parametric mapping method. RESULTS: Major depressed patients with psychotic features showed decreased rCBF in the left subgenual anterior cingulate cortex relative to both non-psychotic patients and healthy controls (P<0.001 one-tailed, uncorrected for multiple comparisons). Relative to the non-psychotic group, depressed patients with psychotic symptoms also had a focus of decreased rCBF in the right inferior frontal cortex, with the voxel of maximal significance in the insula (P<0.031, corrected for multiple comparisons). A similar pattern of significant between-group rCBF differences between psychotic and non-psychotic patients emerged after covarying the analysis for the confounding influence of overall illness severity. CONCLUSIONS: These results provide preliminary evidence that psychotic symptoms in major depression may be associated with abnormalities in ventral paralimbic regions previously implicated in mood regulation and depression.     

Functional imaging of the brain using single photon emission computerized tomography (SPECT)

Summary The use of tracers is an important technique available for studying cerebral function. Changes in signal are large, but as a result of its photon limited nature, the measurement of this signal is limited: spatially, temporally and in terms of accuracy. The most commonly used single photon (SPECT) system (as apposed to positron) is that with a rotating gamma camera, although multi-headed devices and special purpose rings are now also commonly available. The problems of obtaining good functional information are however identical. Firstly the devices need to be optimised in terms of resolution and sensitivity. Secondly several sources of error, notably those associated with scatter, attenuation and limited spatial resolution, need to be corrected, with the aim of obtaining quantitative estimates of radioactivity concentration. Finally such quantitative estimates need to be converted into meaningful estimates of physiological variables by use of an appropriate model. The general aim of many SPECT measurements is to estimate blood flow for example using Tc-99m labelled HMPAO as a tracer. Good results have been obtained in many clinical conditions: stroke, dementia, tumour and epilepsy, for example. Many other tracers are also available, for example to measure density of receptor sites. The use of SPECT in conjunction with other techniques after image registration is suggested as being an essential tool in extracting maximal clinical information.     

Relationship between regional cerebral blood flow and separate symptom clusters of major depression: a single photon emission computed tomography study using statistical parametric mapping

This study examined the relationship between resting regional cerebral blood flow (rCBF) patterns in patients with major depressive disorder (MDD) and specific symptom clusters derived from ratings on the Hamilton Rating Scale for Depression (HRSD) and the Mini Mental State Examination. We hypothesized that the functional activity in frontal, parietal, anterior cingulate, basal ganglia and limbic regions would be related to specific symptom domains. Fifteen patients fulfilling DSM-IV criteria for MDD who were off all psychotropic medications for >4 weeks and 15 normal volunteers were recruited. Single photon emission computed tomography (SPECT) images were obtained after (99m)Tc-ECD injection, and correlations between rCBF patterns and symptom severity ratings were calculated on a voxel-by-voxel basis, using statistical parametric mapping (SPM). Severity of depressive mood was inversely correlated with rCBF in the left amygdala, lentiform nucleus, and parahippocampal gyrus, and directly correlated with rCBF in the right postero-lateral parietal cortex (p < 0.001, uncorrected for multiple comparisons). Insomnia severity was inversely correlated with rCBF in the right rostral and subgenual anterior cingulate cortices, insula and claustrum. Anxiety severity was directly correlated with rCBF in the right antero-lateral orbitofrontal cortex, while cognitive performance was directly correlated with rCBF in the right postero-medial orbitofrontal cortex and in the left lentiform nucleus. Our findings confirmed the prediction that separate symptom domains of the MDD syndrome are related to specific rCBF patterns, and extend results from prior studies that suggested the involvement of anterior cingulate, frontal, limbic and basal ganglia regions in the pathophysiology of MDD.     

Comparison of relative cerebral blood flow maps using pseudo-continuous arterial spin labeling and single photon emission computed tomography

Pseudo‐continuous arterial spin labeling (PCASL) MRI is a relatively new arterial spin labeling technique and has the potential to extend the cerebral blood flow (CBF) measurement to all tissue types, including white matter. However, the arterial transit time (δ_a) for white matter is not well established and a limited number of reports using multi‐delay methods have yielded inconsistent findings. In this study, we used a different approach and measured white matter δ_a (mean ± standard deviation, 1541 ± 173 ms) by determining the arrival times of exogenous contrast agent in a bolus tracking experiment. The data also confirmed δ_a of gray matter to be 912 ± 209 ms. In the second part of this study, we used these parameters in PCASL kinetic models and compared relative CBF (rCBF, with respect to the whole brain) maps with those measured using a single photon emission computed tomography (SPECT) technique. It was found that the use of tissue‐specific δ_a in the PCASL model was helpful in improving the correspondence between the two modalities. On a regional level, the gray/white matter CBF ratios were 2.47 ± 0.39 and 2.44 ± 0.18 for PCASL and SPECT, respectively. On a single‐voxel level, the variance between the modalities was still considerable, with an average rCBF difference of 0.27. Copyright © 2011 John Wiley & Sons, Ltd.     

The pattern of function-related regional cerebral blood flow investigated by single photon emission tomography with 99mTc-HMPAO in patients with presenile Alzheimer's disease and Korsakoff's psychosis

Single photon emission tomography (SPET) with the lipophilic blood flow marker 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO) has been used to determine regional uptake of radiolabel into brain regions of patients with presenile Alzheimer's disease and Korsakoff's psychosis, and age-matched controls. Using occipital cortical uptake as reference area, the pattern of relative regional cerebral blood flow (rCBF) was determined in other cortical areas and basal ganglia. In Alzheimer's disease, reduction in rCBF occurred most strikingly in posterior temporal and parietal areas. By contrast, in Korsakoff's psychosis, posterior temporal rCBF was maintained, although there was a trend to reduced tracer uptake in other cortical areas. These impairments of flow were correlated with impairments of neuropsychological function. In Alzheimer's disease, left posterior temporal and left parietal regions in particular showed rCBF to be strongly correlated with most aspects of cognitive function. In Korsakoff's psychosis, however, impaired flow in frontal regions was correlated with impaired performance on tests of memory and orientation. The findings in Alzheimer's disease show quantitative parallels with those from studies using Positron Emission Tomography (PET), and extend our understanding of the relationship between cognition and regional brain function in dementia. The findings in Korsakoff's psychosis offer the first direct evidence linking frontal lobe dysfunction with the cognitive impairment seen in the disorder.     

Effects of acute hypobaric hypoxia on regional cerebral blood flow distribution: a single photon emission computed tomography study in humans

Single Photon Emission Computed Tomography (SPECT) and radiopharmaceutical stabilizing agents allowed us to investigate regional cerebral blood flow (CBF) distribution in six resting healthy subjects during acute laboratory hypobaric hypoxic conditions. In the hypobaric experiment stabilized 99mTc-D, L-hexamethyl-propylene amine oxime was injected 40 min after reaching hypoxic conditions corresponding to an altitude of 5500 m above sea level. Arterial blood sample was taken after five additional minutes. Mean arterial oxygen pressure and haemoglobin saturation were 28 mmHg and 56%, respectively. The control experiment was performed similarly, apart from barometric pressure and blood gas analysis. We analysed CBF distribution in 12 regions of functional interest bilaterally in frontal, parietal, temporal, occipital cortex, in the hippocampus, in the basal ganglia and other central structures of brain. No overall effect of hypoxia on normalized regional CBF distribution in the considered regions was found. Motor cortex (Brodmann 4) and basal ganglia were the only regions in which hypobaric hypoxia significantly increased relative distribution of the radiopharmaceutical [F(1,5)=18.30; P < 0.008 and F(1,5)=10.85; P < 0.022, respectively]. Despite severe hypoxia, we did not observe any major regional CBF redistribution. We found a small relative increase in blood flow to the motor cortex and the basal ganglia, at rest after 40 min of hypobaric hypoxia, suggesting a preferential compensatory mechanism of these functional regions of brain.     

Rapid measurement of regional cerebral blood flow in the baboon using15O-labelled water and dynamic positron emission tomography

The sensitivity and reproducibility of rapid measurements of regional cerebral flow (rCBF) using a bolus injection of H₂ ¹⁵O and dynamic positron emission tomography (PET) were investigated in anaesthetised baboons. The cerebrovascular reactivity to changes in arterial pCO₂ was used as an experimental support. PET data were acquired over 4 min following a single bolus intravenous injection of H₂ ¹⁵O, while arterial blood was withdrawn for continuous activity counting. Images were reconstructed with a dynamic sequence of 45×2s+15×10s, including a correction for decay. Regional values of CBF were derived from non-linear least-squares fits of the time activity curves using a four-parameter two-compartment model. The results obtained with a four-parameter fitting method were compared with those obtained with two other rapid estimation methods, first fitting two parameters only, CBF and partition coefficient (p), and secondly autoradiography (with p fixed at 0·95 ml brain ml blood⁻¹). Twelve regions of interest were analysed. The values for the basal CBF obtained from 13 measurements in two baboons were close to published values obtained with other techniques. Reproducibility checks showed a mean variation of 9·7 per cent. The CBF measurements performed in hypercapnic conditions gave results similar to published data in other animal species, showing a 4·5±0·9 per cent increase in CBF per mm Hg p_aCO₂. The results obtained with the three estimation techniques were closely correlated. The dynamic bolus H₂ ¹⁵O method appeared to be suitable for high blood flow measurements.     

Assessment of regional cerebral blood flow (rCBF) in ischemic stroke using Tc-99m HMPAO SPECT--comparison with CT and MR findings

To assess the regional cerebral blood flow (rCBF) in ischemic stroke, we analyzed the findings of single photon emission computed tomography (SPECT) using technetium-99m hexamethyl propyleneamine oxime (Tc-99m HMPAO). The SPECT images revealed abnormal areas of decreased perfusion in 29 out of 31 subjects (93.5%), which represented a higher detection rate than those for CT and MR (89.5%, respectively). Also, the areas of decreased perfusion were frequently larger than the lesions on CT and MR. Areas of decreased perfusion remote from the CT/MR lesions were found in 10 patients, including 8 with crossed cerebellar diaschisis (CCD). Thus, studies of rCBF by Tc-99m HMPAO SPECT can be useful in the assessment of ischemic stroke.