Parietal Perfusion Research Articles

Emission tomography in dementia

Dementia is a chronic brain syndrome with enormous impact on health care provision. Emission tomography (single photon emission computed tomography (SPECT) and positron emission tomography (PET)) provides a unique tool to investigate functional and neurochemical changes, both in those with established dementia and in those at risk of subsequent cognitive decline. Alzheimer's disease is characterized by bilateral temporoparietal hypoperfusion on SPECT and hypometabolism on PET, which may precede the onset of dementia as similar changes can be demonstrated in those with mild cognitive impairment and in those genetically at risk of developing Alzheimer's disease. In dementia with Lewy bodies medial parietal and occipital perfusion deficits are seen together with pre-synaptic and post-synaptic dopaminergic changes, most particularly a reduction in the striatal pre-synaptic dopamine transporter which can be visualized using appropriate ligands (e.g., (123)I-FP-CIT). Vascular dementia is associated with multiple, asymmetric, perfusion deficits in multi-infarct dementia. In contrast, subcortical vascular dementia is associated with reduced perfusion but preserved oxygen extraction fraction on PET. Fronto-temporal dementia is characterized by both hypometabolism and hypoperfusion in fronto-temporal lobes, though hypometabolism appears more extensive, affecting large areas of the cerebral hemispheres. Longitudinal studies of treatment response in Alzheimer's disease with cholinergic drugs have found changes in regional blood flow and nicotinic and muscarinic receptor function in those patients who respond to treatment. Currently, emission tomography is widely used for assisting with clinical differential diagnosis. Future developments will entail the development and application of more specific neurochemical ligands and those which bear a closer relationship to the underlying disease processes, including markers of tau, amyloid and synuclein pathology.

N-isopropyl-p-123I Iodoamphetamine Single Photon Emission Computed Tomography Study of Parkinson's Disease with Dementia

Intellectual deterioration occurs in 10-40% of patients with Parkinson's disease. However, there are many conflicting studies on its relation with brain perfusion and the nature of this dementing process remains controversial. To compare cortical perfusion by SPECT using (123)I-IMP between Parkinson's disease patients with dementia and those without dementia and to investigate the correlation between dementia in Parkinson's disease and brain perfusion in various areas. Fifty-two cases of Parkinson's disease and 10 control cases were studied. The Parkinson's disease with dementia group included 30 cases and the Parkinson's disease without dementia group included 22 cases. By multiple logistic regression method, we demonstrated significant hypoperfusion in the occipital cortex in Parkinson's disease with dementia. The cause of dementia in Parkinson's disease may vary. We demonstrated that occipital hypoperfusion was closely correlated to dementia in Parkinson's disease compared to frontal, parietal and temporal perfusion.

Predicting the accuracy of a diagnosis of Alzheimer's disease with 99mTc HMPAO single photon emission computed tomography

The current clinical practice of reporting images obtained with single photon emission computed tomography (SPECT) with 99mTc- d,l-hexamethylpropylene amine oxime ( 99mTc HMPAO) images was examined by having 16 experts evaluate the appearance of SPECT images in patients with probable Alzheimer type dementia (ATD), patients with major depressive episode (DSM-IV), and healthy volunteers. The experts rated diagnostic criteria of scan appearance in respect of importance for their individual diagnostic practice. Experts were nuclear medicine specialists, psychiatrists and physicists taking part in a European multi-centre collaborative project. They examined 158 perfusion scans and then the same perfusion scans together with statistical parametric maps (SPMs). The sensitivity of experts’ diagnostic judgments was significantly and negatively correlated with the importance they attributed to reduced regional perfusion in the parietal lobes. A corresponding positive correlation was observed for diagnostic specificity against depressed and healthy volunteers. Similar results were observed with SPMs, where in addition area under the receiver operating characteristic (ROC) curve was significantly reduced with raters’ increased diagnostic reliance on frontal lobe perfusion deficits. Sensitivity was greater with SPM for patients younger than 70 years and with dementia severity. The more importance experts placed on parietal (symmetrical) perfusion deficits, the less sensitive and the more specific their diagnostic judgment was. Using multiple raters in large patient samples may provide a way of identifying successful explicit diagnostic strategies for clinical image analysis.

Single-dose ebselen does not afford sustained neuroprotection to rats subjected to severe focal cerebral ischemia

Oxygen free radicals have been involved in the pathophysiology of cerebral ischemia, especially after spontaneous or thrombolytic reperfusion. In this study with rats, we have combined a severe focal ischemic insult (2 h) and a prolonged reperfusion time (7 days) to assess the possible sustained neuroprotective effect of ebselen (10 or 100 mg/kg), a small, lipophilic organoselenium compound which mimics glutathione peroxidase. Parietal cortical perfusion was measured by laser-Doppler flowmetry, and focal cerebral ischemia was carried out by the intraluminal thread method. We have measured plasma selenium levels, brain reduced glutathione levels, as a marker of oxidative stress, and infarct volume associated with cerebral ischemia. Focal ischemia did not alter reduced glutathione levels, while 60 min reperfusion following ischemia induced a significant ( P<0.05) decrease in reduced glutathione levels of the ipsilateral hemisphere. Pretreatment with ebselen, which induced significant ( P<0.05) increase in plasma selenium levels, did not significantly alter the decrease in reduced glutathione levels. The ischemic insult induced 30% mortality on average, with deaths always occurring within 12–48 h. Surviving rats suffered up to 25% body weight loss 1 week after the ischemic insult. Infarct volumes were 26.8±4.7% of the hemisphere in placebo-treated rats, 26.6±3.6% in 10 mg/kg ebselen-treated rats, and 25.6±6.4% in 100 mg/kg ebselen-treated rats (not significantly different). Single-dose administration of ebselen does not reduce the size of brain infarct resulting from severe focal cerebral ischemia in rats. In contrast to previous studies with relatively earlier endpoints, we have delayed the measurement of infarct volume to 1 week after the ischemic insult.

Use of Photoplethysmography to Determine Gastrointestinal Perfusion Pressure: An Experimental Canine Model

Objectives: To develop an experimental model to assess the parietal perfusion pressure (PPP) of the digestive tract using photoplethysmography. Materials and Methods: Twenty-two mongrel dogs were used. Progressive external compression was applied to the intestinal wall and the PPP was assessed with photoplethysmography. The study group was divided into two groups. In group 1 PPP was measured at the levels of the stomach, duodenum, jejunum and transverse colon. In group 2 PPP was measured after temporary occlusion of the truncal and marginal circulation of the jejunum to provide further variables. Results: The PPP decreased significantly for each successive distal section. Correlation coefficients and indices for PPP and mean arterial pressures were statistically significant (p < 0.005). Truncal occlusion provoked a drop in PPP whereas marginal occlusion scarcely modified the basal results. Conclusions: Photoplethysmography, through measurements of the residual arterial wave amplitude, is a valid method of determining quantitatively the PPP of the digestive tract and could be useful in a clinical environment.

Progesterone exacerbates striatal stroke injury in progesterone-deficient female animals.

We have previously shown that female animals experience substantial protection from brain injury after reversible middle cerebral artery occlusion (MCAO) compared with their male or ovariectomized female counterparts. The reproductive steroid estrogen has been shown to provide neuroprotection from a variety of experimental insults, but the importance of progesterone as an anti-ischemic treatment has not been well explored. We evaluated histological outcomes after MCAO in ovariectomized female rats with or without acute or chronic progesterone replacement therapy. Age-matched, adult female Wistar rats were ovariectomized and treated with 0, 30, or 60 mg/kg progesterone IP 30 minutes before ischemia (n=12 to 14 per group) or with 30 mg/kg progesterone IP daily for 7 to 10 days before ischemia (n=16). Each animal subsequently underwent 2 hours of MCAO with the intraluminal filament technique, followed by 22 hours of reperfusion. Ipsilateral parietal cortex perfusion was monitored with laser Doppler flowmetry throughout ischemia. Cortical, caudate-putamen, and hemispheric infarction volumes were determined with 2,3,5-triphenyltetrazolium chloride staining and digital image analysis. Intraischemic plasma progesterone levels were 5+/-3, 102+/-20,* 181+/-28,* and 133+/-25* ng/mL in the 0, 30, and 60 mg/kg acute progesterone group and the 30 mg/kg chronic progesterone group, respectively (*P<0.05 compared with 0 mg/kg). Caudate-putamen infarction volume (percent contralateral structure) was significantly increased by chronic progesterone treatment: 45.6+/-5.1%* in the 30 mg/kg chronic progesterone group and 29.2+/-5.3%, 35.8+/-5.1%, and 42.0+/-5.0% in the 0, 30, and 60 mg/kg acute progesterone groups, respectively (*P<0.05 compared with 0 mg/kg). Cortical and total hemispheric infarction volumes (percent contralateral structure) were unchanged by progesterone treatment. Exogenous progesterone therapy does not ameliorate histological injury after MCAO in previously ovariectomized, adult female rats. Furthermore, chronic progesterone administration can exacerbate infarction in subcortical regions.

Reduction of infarct size by the NO donors sodium nitroprusside and spermine/NO after transient focal cerebral ischemia in rats

Nitric oxide (NO) plays a dual role (neuroprotection and neurotoxicity) in cerebral ischemia. NO promoting strategies may be beneficial shortly after ischemia. Therefore, we have studied the hemodynamic and possible neuroprotective effects of two NO donors, the classical nitrovasodilator sodium nitroprusside (SNP) and the NONOate spermine/NO, after transient focal cerebral ischemia in rats. Parietal cortical perfusion was measured by laser-Doppler flowmetry. The effects of increasing intravenous doses (10–300 μg) of sodium nitroprusside and spermine/NO on cortical perfusion and arterial blood pressure were assessed. Transient (2 h) focal cerebral ischemia was carried out by the intraluminal thread method. The effects of intraischemic intravenous infusion of SNP (0.11, 1.1 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) on hemodynamic parameters and infarct size developed after 1 week reperfusion were assessed. In control conditions, SNP and, to a lesser extent, spermine/NO induced dose-dependent hypotension and concomitant reduction in cortical perfusion. In focal cerebral ischemia, infusion of SNP (0.11 mg/kg) and spermine/NO (0.36, 3.6 mg/kg) reduced the infarct size. In the case of spermine/NO, cortical perfusion was maintained above the control levels during the ischemic insult. No significant hypotension was elicited by NO donors at the dose-ratios infused. In conclusion, brain damage induced by transient focal ischemia is reduced by intravenous NO donors. Neuroprotective effects of spermine/NO are due at least in part to improvement of brain perfusion, while sodium nitroprusside must provide direct cytoprotection. These results give further support to the protective effect of NO in the early stages of cerebral ischemia and point to the therapeutic potential of NONOates in the management of brain ischemic damage.

Cerebral blood flow patterns underlying the differential impairment in category vs letter fluency in Alzheimer’s disease

Verbal fluency tasks are used to assess language functioning in Alzheimer’s disease (AD), and performance typically declines as the disease progresses. However, several studies have shown that Category Fluency performance (produce words from a category) declines faster than Letter Fluency performance (produce words beginning with a certain letter), which is not the case for other dementias. The purpose of this study was to determine if each of these two types of fluency tasks was associated with different patterns of cerebral blood flow abnormality in AD. A resting, Xenon-inhalation regional cerebral blood flow measurement ( 133Xe rCBF) and neuropsychological evaluation was administered to 25 patients with probable AD and 24 healthy elderly controls. Stepwise regression using rCBF measures as predictor variables was used to predict Category and Letter Fluency performance, in both a combined group of patients and controls, and in the patient group alone. Correlations were also computed between rCBF variables and the difference between normatively corrected scores on each task for each subject, which characterized the extent of the discrepancy between them. In full sample regressions, both Category and Letter Fluency were predicted by education and the decline in left inferior parietal flow, a focal AD-related deficit. Additional variance in Category fluency, however, was predicted by global mean flow, while additional variance in Letter Fluency was predicted by frontal flow. Within the patient sample, in turn, the primary predictor of Category Fluency was mean flow; the primary predictor of Letter Fluency was left-sided frontal flow. Analysis of the fluency difference score revealed that relatively greater impairment of Category Fluency was associated with more typical, AD-related deficits in posterior temporal and parietal perfusion. When the two were equivalently impaired, typical AD-related deficits were accompanied by marked deficits in frontal perfusion. These findings are consistent with the underlying neuropsychology of these tasks, and suggest that Category Fluency’s stronger association to the most typical CBF deficits of AD account for its greater sensitivity to this disease. Letter Fluency deficits, on the other hand, carry significant information about the degree to which perfusion deficits have spread to frontal cortex.

Cerebral blood flow changes in patients with conversion disorder

We evaluated regional cerebral blood flow in five patients with conversion disorder (three females, two males, mean age±S.D.: 29.8±9.5 years) with astasia-abasia. The patients underwent single photon emission computed tomography after the injection of 555 MBq of [ 99mTc]hexamethylpropyleneamine oxime. Uptake ratios between areas of decreased perfusion and normal brain regions were considered significantly decreased when there was a change ≥10%. Four of the five patients had left temporal and one patient had left parietal perfusion decreases. Uptake ratios ranged from 0.72 to 0.88 (mean±S.D.: 0.81±0.08). Our findings suggest that alterations in regional brain perfusion may accompany conversion symptoms. Functional imaging may therefore offer a means of elucidating the neural correlates of conversion disorder.

Spatial- and object-based attentional deficits in Alzheimer's disease. Relationship to HMPAO-SPECT measures of parietal perfusion.

The purpose of this study was to investigate the ability of patients with Alzheimer's disease to shift attention between spatial locations and between objects, and to examine the brain regions involved in these cognitive operations using single photon emission computed tomography (SPECT) imaging. A recent study of patients with focal lesions provided evidence that the right and left parietal lobes are differentially involved in shifting selective attention from invalidly cued spatial locations and objects, respectively (Egly et al. J Exp Psychol Gen 1994; 123: 161-77). Accordingly, in Alzheimer's disease patients, we hypothesized that right parietal hypoperfusion on SPECT would be associated with deficits on the spatial-based component of a cued reaction time task, and left parietal hypoperfusion would be associated with the deficits on the object-based component. Attentional performance of Alzheimer's disease patients (n = 29) was compared with aged-matched normal controls (n = 17) using a cued reaction time task based on Egly et. al. (1994). Regions of interest were defined semi-automatically on SPECT, and were anatomically localized with the aid of co-registered MRI. As hypothesized, in Alzheimer's disease patients, reaction time costs of invalid targets eliciting shifts of attention between spatial locations were selectively correlated with SPECT hypoperfusion in the right superior parietal lobe; while reaction time costs of between-object shifts of attention were correlated with hypoperfusion in the left inferior parietal lobe. These results provide evidence for the specialized roles of the right and left parietal regions in the spatial and object components of attentional shifting respectively, and suggest that the cognitive profile associated with Alzheimer's disease includes both spatial- and object-based attentional impairments.

Severe Retrograde Amnesia After a Mild Closed Head Injury

Abstract We describe a patient (RP) who developed a severe retrograde amnesia in the absence of anterograde memory deficits after a minor closed head injury. The retrograde amnesia affected RP's autobiographical memory as well as his memory for famous people, well known events and semantics. He showed no structural brain lesion on the MRI, but a SPECT study showed right frontal, parietal and thalamlc perfusion deficit. While RP could partially relearn some of the lost memories, 1 year after the accident he still showed a dense retrograde amnesia. Our case demonstrates that severe and long-lasting retrograde memory deficits may occur after a ‘minor’ closed head injury.

Severe retrograde amnesia after a mild closed head injury

We describe a patient (RP) who developed a severe retrograde amnesia in the absence of anterograde memory deficits after a minor closed head injury. The retrograde amnesia affected RP's autobiographical memory as well as his memory for famous people, well known events and semantics. He showed no structural brain lesion on the MRI, but a SPECT study showed right frontal, parietal and thalamlc perfusion deficit. While RP could partially relearn some of the lost memories, 1 year after the accident he still showed a dense retrograde amnesia. Our case demonstrates that severe and long-lasting retrograde memory deficits may occur after a ‘minor’ closed head injury.

Inferior Parietal Perfusion, Lateralization, and Neuropsychological Dysfunction in Alzheimer's Disease

The severity of inferior parietal perfusion deficits in Alzheimer's disease (AD) is strongly associated with global intellectual decline. The relationship to specific losses of neuropsychological functioning, however, is less clear, as is the relative importance of the side (left vs. right) of hemispheric deficit. In this study, 53 patients with probable AD and 35 elderly controls received both a resting133Xe rCBF measurement and neuropsychological examination. AD patients demonstrated the expected bilateral deficits in inferior parietal perfusion, as well as impairment on measures of mental status, intelligence, verbal and visual memory, attention, language, and construction abilities. The severity of this bilateral parietal deficit, in turn, was associated with virtually all of these AD-related neuropsychological impairments, most strongly with declining Performance IQ. Left-sided deficits correlated better with overall declines in IQ, as well as with declining attention and language fluency. Right-sided deficits, on the other hand, correlated best with declines in mental status and—paradoxically—verbal memory and contributed independently to declines in Full Scale and Performance IQ. In terms of the number and strength of their association to neuropsychological measures, left-sided deficits appear much more predictive of cognitive decline in AD. Right-sided deficits, however, may be most important for predicting aspects of performance skill that are only indirectly assessed in standard paper-and-pencil format. Overall, it appears that both sides make significant, but independent contributions to general functional decline in AD, but that left-sided deficits are more closely associated with cognitive decline as measured by most standard neuropsychological measures.

Single photon emission computed tomography in dementia: relationship of perfusion to cognitive deficits.

Sixteen patients with dementia (nine with Alzheimer's disease and seven with multi-infarct dementia) were studied with xenon-133 and hexamethyl-propyleneamine-oxime single photon emission computed tomography (SPECT). Quantification of cerebral blood flow was determined in 16 hemispheric regions of interest. Neuropsychological deficits were assessed with the Mini-Mental State Examination and the Neurobehavior Cognitive Status Examination. Alzheimer's disease patients had symmetric reduction of parietal lobe perfusion; multi-infarct dementia patients had multifocal perfusion deficits. Correlations were demonstrated between cerebral blood flow in the posterior brain regions and performance on tests of language, memory, attention, figure copying, judgment, and similarities. Alzheimer's disease patients exhibited more language impairment than multi-infarct dementia patients. SPECT promises to provide diagnostic information and data relevant to interpretation of neuropsychological deficits.

Single‐Photon Emission Computed Tomographic Perfusion Imaging in Autopsy‐Diagnosed Dementia

Physiological imaging of regional cerebral blood flow with single‐photon emission computed tomography (SPECT) has been proposed to be diagnostically useful in the evaluation of patients with dementia because of the frequent finding of temporal and parietal lobe hypoperfusion in patients with Alzheimer's disease (AD). A major limitation of SPECT to date has been the selection of patients using clinical criteria, which may be unreliable in excluding patients with non‐Alzheimer dementias from study. SPECT with the perfusion tracer 123l‐N‐isopropyl‐p‐iodoamphetamine was used to study 16 dementia patients who were subsequently followed to autopsy, as well as 16 elderly control subjects. Eleven dementia patients had the diagnosis of AD confirmed by autopsy, while 5 had other, nonAD dementias. SPECT perfusion patterns were evaluated as regional ratios of lobar radioactivity counts normalized to either activity counts in the occipital lobes (occipital ratio) or activity counts in the entire tomographic slice (whole‐slice ratio). Results showed that the relative frontal perfusion differentiated non‐AD patients from control subjects and AD patients regardless of which ratio method was used, while temporal and parietal relative perfusion ratios were more effective at differentiating AD from non‐AD patients when the whole‐slice ratio was used, although the ratio used did not affect the differentiation of AD patients from control subjects. Scatterplots of the whole‐slice ratio in the right parietal and left temporal lobes showed no overlap between AD and non‐AD patients and control subjects. These results support the diagnostic utility of SPECT in the clinical evaluation of dementia patients, particularly in distinguishing AD from non‐AD dementias during life.

Patterns of regional cerebral blood flow in Alzheimer's disease.

Regional cerebral blood flow was assessed in 35 patients with Alzheimer's disease and the same number of matched normal volunteers. Images were scored for regional perfusion deficits. Mildly demented patients had parietal and temporal perfusion deficits, often unilateral. Moderate to severely demented patients had bilateral temporal and parietal perfusion deficits. All severely demented patients also had involvement of both occipital regions. Frontal lobe deficits were seen in 14 patients. Left cortical perfusion deficits were more severe than the right cortical perfusion deficits in general. Patients with early onset of the disease showed left frontal deficits, more often, however, the total perfusion deficit scores in early and late onset groups were not statistically significant. Also, the cognitive performance scores were not statistically significant in these two groups. These results suggest a stage-dependent reduction in regional cerebral blood flow in patients with Alzheimer's disease.

Assessing Utility of Single Photon Emission Computed Tomography (SPECT) Scan in Alzheimer Disease

Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.

99mTc]-HM-PAO SPECT in Parkinson's disease.

Thirty-six patients affected by Parkinson's disease were studied using single photon emission computed tomography (SPECT) and [99mTc]-HM-PAO as a tracer. The scanning procedure was performed 16-24 h after discontinuation of specific therapy. Tracer activity ratios were determined in 10 pairs of cerebellar, cortical, and subcortical regions. Data were compared with those of 10 age-matched controls. Most of the regions examined did not show any relevant change between parkinsonian and control subjects. Notably, mean activity in striatal regions were similar in the two groups. Increased activity in caudate-putamen was found in patients who were on chronic DOPA therapy. Side-to-side asymmetries in the basal ganglia increased with the severity of the disease. Significant reductions of tracer uptake, from control values, were observed bilaterally in the parietal cortex. These deficits were more pronounced in patients with mental deterioration and in subjects who had been chronically treated with anticholinergic drugs. Parietal perfusion deficits in parkinsonian patients resemble those described in Alzheimer's dementia. These findings suggest that the heterogeneous alterations of regional cerebral blood flow (rCBF) in parkinsonian patients reflect the multifactorial pathophysiology of the disease.