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A 62-year-old woman was referred for SPECT brain blood flow study with a diagnosis of possible dementia or depression. Findings within the brain were noncontributory, but extraneous structures with high blood flow were detected within the soft tissues of temporal regions and face. On questioning, the patient stated that she had sleep bruxism, with gnashing and grinding of her teeth. This did not occur during waking. Bruxisms and its consequences, with effects on the teeth and jaws, are a problem of importance to oral surgeons and dentists. There is considerable active research into methods of treatment of sleep bruxism.

The purpose of this study is to determine the value of Tc-99m HMPAO SPECT in the diagnosis of the dementias. Tc-99m HMPAO was used with a 3-camera scanner to produce 5 sets of sectional images of the brain. Images were further processed using Statistical Parametric Mapping. Diagnosis was made by a physician blinded to the clinical diagnosis. Results in 73 subjects were compared with a neuropathologic study of the brain at autopsy. Data were analyzed for sensitivity, specificity, positive and negative predictive values and accuracy. These results are compared with several other studies performed with Tc-99m HMPAO SPECT with histopathologic correlation. This procedure is widely available and relatively inexpensive and may be of value in patients with dementias and problematic diagnoses. Further, a degree of differential diagnosis between Alzheimer's and Frontotemporal diseases may be effected. The study was approved by our Institutional Review Board.

Detecting aggregated amyloid peptides (Abeta plaques) presents targets for developing biomarkers of Alzheimer's disease (AD). Polymeric n-butyl-2-cyanoacrylate (PBCA) nanoparticles (NPs) were encapsulated with radiolabelled amyloid affinity (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) as in vivo probes. (125)I-CQ-PBCA NPs crossed the BBB (2.3 +/- 0.9 ID/g) (P < .05) in the WT mouse (N = 210), compared to (125)I-CQ (1.0 +/- 0.4 ID/g). (125)I-CQ-PBCA NP brain uptake increased in AD transgenic mice (APP/PS1) versus WT (N = 38; 2.54 x 10(5) +/- 5.31 x 10(4) DLU/mm(2); versus 1.98 x 10(5) +/- 2.22 x 10(4) DLU/mm(2)) and in APP/PS1/Tau. Brain increases were in mice intracranially injected with aggregated Abeta(42) peptide (N = 17; 7.19 x 10(5) +/- 1.25 x 10(5) DLU/mm(2)), versus WT (6.07 x 10(5) +/- 7.47 x 10(4) DLU/mm(2)). Storage phosphor imaging and histopathological staining of the plaques, Fe(2+) and Cu(2+), validated results. (125)I-CQ-PBCA NPs have specificity for Abeta in vitro and in vivo and are promising as in vivo SPECT ((123)I), or PET ((124)I) amyloid imaging agents.

A survey of research activity on nanoparticles (NPs) based on polymeric devices that could cross the blood-brain barrier (BBB) is given along with the presentation of our own data on the development of NPs of n-butyl-2-cyanoacrylate (BCA) for brain delivery to aid the early diagnosis of Alzheimer's disease (AD), a neurodegenerative disorder of the elderly people, the most prevalent form of dementia. Typical data are presented on in vivo detection of amyloid peptides (A beta) (amyloid plaques) that are used as targets for developing the biological markers for the diagnosis of AD. In order to develop efficient in vivo probes, polymeric n-butyl-2-cyanoacrylate (PBCA) NPs have been prepared and encapsulated with the radio-labeled amyloid affinity drug (125)I-clioquinol (CQ, 5-chloro-7-iodo-8-hydroxyquinoline) to improve the transport to brain and amyloid plaque retention of (125)I-CQ using the NPs of PBCA. The (125)I-CQ discriminately binds to the AD post-mortem brain tissue homogenates versus control. (125)I-CQ-PBCA NPs labeled the A beta plaques from the AD human post-mortem frontal cortical sections on paraffin-fixed slides. Storage phosphor imaging verified preferential uptake by AD brain sections compared to cortical control sections. The (125)I-CQ-PBCA NPs crossed the BBB in wild type mouse, giving an increased brain uptake measured in terms of % ID/g i.e., injected dose compared to (125)I-CQ. Brain retention of (125)I-CQ-PBCA NPs was significantly increased in the AD transgenic mice (APP/PS1) and in mice injected with aggregated A beta 42 peptide versus age-matched wild type controls. The results of this study are verified by in vivo storage phosphor imaging and validated by histopathological staining of plaques and select metal ions, viz. Fe(2+) and Cu(2+). The (125)I-CQ-PBCA NPs had more efficient brain entry and rapid clearance in normal mice and enhanced the retention in AD mouse brain demonstrating the ideal in vivo imaging characteristics. The (125)I-CQ-PBCA NPs exhibited specificity for A beta plaques both in vitro and in vivo. This combination offered radio-iodinated CQ-PBCA NPs as the promising delivery vehicle for in vivo single photon emission tomography (SPECT) ((123)I) or PET ((124)I) amyloid imaging agent. The importance of the topic in relation to brain delivery and other similar type of work published in this area are covered to highlight the importance of this research to medical disciplines., ((c) 2009 John Wiley & Sons, Inc.)

Several case definitions of chronic illness in veterans of the 1991 Persian Gulf War have been linked epidemiologically with environmental exposure to cholinesterase-inhibiting chemicals, which cause chronic changes in cholinergic receptors in animal models. Twenty-one chronically ill Gulf War veterans (5 with symptom complex 1, 11 with complex 2, and 5 with complex 3) and 17 age-, sex- and education-matched controls, underwent an 99mTc-HMPAO-SPECT brain scan following infusion of saline and >48 h later a second scan following infusion of physostigmine in saline. From each SPECT image mean normalized regional cerebral blood flow (nrCBF) from 39 small blocks of correlated voxels were extracted with geostatistical spatial modeling from eight deep gray matter structures in each hemisphere. Baseline nrCBF in symptom complex 2 was lower than controls throughout deep structures. The change in nrCBF after physostigmine (challenge minus baseline) was negative in complexes 1 and 3 and controls but positive in complex 2 in some structures. Since effects were opposite in different groups, no finding typified the entire patient sample. A hold-out discriminant model of nrCBF from 17 deep brain blocks predicted membership in the clinical groups with sensitivity of 0.95 and specificity of 0.82. Gulf War-associated chronic encephalopathy in a subset of veterans may be due to neuronal dysfunction, including abnormal cholinergic response, in deep brain structures.

Purpose: The purpose of this study is to determine the value of Tc-99m HMPAO SPECT in the diagnosis of the dementias, with particular reference to Alzheimer disease., Materials and Methods: Tc-99m HMPAO was used with a 3-camera scanner to produce 5 sets of sectional images of the brain. Diagnosis was made by a physician blinded to the clinical diagnosis. Results in 49 subjects were ultimately compared with neuropathologic study of the brain at autopsy., Results: Sensitivity = 86.7% (68.4-95.6%, 95% confidence interval [CI]), specificity = 89.5% (65.5-98.2% CI), positive predictive value = 92.9% (75.0-98.8% CI), negative predictive value = 81% (57.4-93.7% CI), accuracy = 87.8% (74.5-94.9% CI), likelihood ratio = 8.23% (7.09-9.57% CI)., Conclusions: Comparison is made with several other SPECT and PET series with histopathologic correlation. Brain blood flow SPECT is useful in the diagnosis and differential diagnosis of the dementias.

The characterization of frontotemporal lobar degeneration (FTLD) is complicated and not widely recognized. Connected language measures (ie, discourse) and functional neuroimaging may advance knowledge specifying early distinctions among frontal dementias. The present study examined the correspondence of discourse measures with (1) clinical diagnosis and (2) single photon emission computed tomography (SPECT) imaging. Nineteen subjects were selected from Alzheimer's Disease Center (ADC) participants if they were diagnosed with early-stage frontotemporal lobar degeneration and also underwent single photon emission computed tomography and discourse evaluation. First, clinical diagnoses given by specialists at an Alzheimer's Disease Center were compared with the discourse-based diagnostic profiles. Secondly, compromised brain regions that were predicted from discourse profiles were compared with SPECT findings. Results revealed a significant correspondence between the ADC diagnosis and the discourse-based diagnoses. Also, the discourse profiles across frontotemporal lobar degeneration subtypes were consistently associated with distinctive patterns of SPECT hypometabolism in the right frontal, left frontal, or left temporal lobes. These findings suggest that discourse methods may be systematized to provide an efficient adjunct measure beyond the traditional word and sentential level measures. Objectifying complex language performance may contribute to early detection and differentiation among frontotemporal lobar degeneration variants because consensus in the literature states that language is a core disturbance of frontotemporal lobar degeneration.

Unlabelled: This was a study to evaluate the posterior cingulate sign in differential diagnosis between Alzheimer's and frontotemporal disease. The impending availability of effective treatment for Alzheimer's disease makes this differential diagnosis important., Methods: Images of 20 patients with clinically confirmed or autopsy-proven (10 patients) Alzheimer's disease and 20 patients with clinically confirmed or autopsy-proven (7 patients) frontotemporal disease were compared with the consolidated images of 20 elderly healthy control subjects. The (99m)Tc-hexamethylpropyleneamine oxime SPECT data on brain blood flow from each patient were compared with the consolidated control image using statistical parametric mapping., Results: Sixteen of 20 patients with Alzheimer's disease showed the posterior cingulate sign in the form of significant blood flow reductions; 1 of 20 patients with frontotemporal disease showed the posterior cingulate sign. That patient's illness has evolved into Alzheimer's disease. The remaining 19 patients were negative for the posterior cingulate sign., Conclusion: When present, the posterior cingulate sign indicates the presence of Alzheimer's disease; it is apparently absent in frontotemporal disease, thus serving as a differential diagnostic sign. It was absent in 3 patients with proven tangle-predominant Alzheimer's disease.

Lateralization on neuroimaging was compared in cases of frontotemporal lobar degeneration (FTLD; n = 10) and cases of definite Alzheimer's disease (AD; n = 17). All of the cases were pathologically confirmed and semi-quantitative and statistical parametric mapping methods were employed. Seven of the 10 FTLD cases had lateralization on at least one neuroimaging modality: single photon emission computerized tomography (SPECT), MRI, or CT. All 6/6 FTLD cases with SPECT showed lateralization. MRI results generally agreed with SPECT findings. Three of 4 FTLD cases had lateralized atrophy on CT. For the AD cases, 10/17 SPECTs, 2/7 MRIs, and 1/9 CTs showed lateralized findings. Of the neuroimaging modalities utilized, SPECT was the most sensitive in detecting lateralization., (Copyright 2004 S. Karger AG, Basel)

This is the first report of fMRI in monozygotic twins discordant for AD. FMRI brain activation patterns were examined during visuospatial and verbal working memory tasks. The affected twin had greater parietal involvement bilaterally during both working memory tasks and reduced left dorsolateral prefrontal cortex activity on the visuospatial memory task. Thus, fMRI may identify additional brain regions recruited in patients with AD to perform a given cognitive task.

In this study we tested the hypothesis that synapse loss contributes to decreased regional cerebral blood flow (rCBF) in Alzheimer disease (AD). We compared antemortem rCBF and postmortem analysis of synaptophysin, as a measure of synapse loss, in 13 cases of AD. rCBF studies were performed using inhaled xenon gas (Xe-133), which yields quantitative results. Synapse loss was evaluated in postmortem brain samples using an enzyme-linked immunosorbant assay (ELISA) that measures synaptophysin, with results expressed as picomoles synaptophysin/10 mg brain. Synaptophysin was expressed either as concentration (QS method) or as the ratio of the concentration to the combined results in frontal, temporal and parietal lobe (RS method). There was no correlation between synapse loss and rCBF using the QS method and only borderline significance between right SPECT and right temporal synaptophysin using the RS method. The results of this study suggest that synapse loss may be a minor contributor to the decreased rCBF observed in AD., (Copyright 2003 S. Karger AG, Basel)

Unlabelled: Occipital lobe perfusion defects have been identified on regional cerebral blood flow (rCBF) SPECT scans of adolescent children and young adults with major depressive disorder (MDD). We reinvestigated a series of rCBF SPECT scans obtained several years ago on drug-naive children with a clinical diagnosis of MDD and on healthy children., Methods: To test whether visually apparent abnormalities in rCBF constitute statistically significant differences between patients, given the relatively small sample sizes, we applied the technique of statistical parametric mapping (SPM)., Results: Two groups of patients were identified: 8 with significant posterior flow deficits in the occipital cortex (Brodmann's areas 18 and 19), usually symmetric, and best visualized on paramedian sagittal sections, and 13 without obvious occipital perfusion deficits but with anterior rCBF deficits in a pattern often described in the literature, attaining statistical significance in the right frontal region. Other localizations in the left frontal and bilateral prefrontal regions did not attain significance, but each localization contained statistically significant maxima (z scores). The scan findings of all 18 healthy children were normal., Conclusion: With the aid of SPM, 2 groups of children with significantly different rCBF behavior were identified. The reason for this difference is not known but should be investigated to determine its possible significance to patients with MDD.

Background: Adult polyglucosan body disease (APBD) is a rare disorder, presenting with varying combinations and severity of upper and lower motor neuron dysfunction, sensory deficits, dementia, and urinary incontinence. Onset is in the 40s or 50s. The diagnosis is made by finding polyglucosan bodies (PB) in histologic sections of brain or spinal cord, peripheral nerve, or dermal sweat glands. Although 2 pairs of the 22 previously reported cases were siblings, the familial nature of the disease has not been emphasized., Methods: We report 2 adult siblings, a male and a female, each of whom had the clinical diagnosis of vascular dementia. Both were confirmed at autopsy to have APBD. We characterized the lesions in autopsy tissues using a battery of histological stains, lectin histochemistry, and electron microscopy., Results: Innumerable PB were distributed throughout brain, heart, skeletal muscle, liver, and dermal sweat glands. PB were highlighted by periodic acid Schiff stain and concanavalin A lectin. Ultrastructurally, PB were composed of aggregates of filaments within axons and astrocytic processes, and lying free in the neuropil, but not within neuronal perikarya., Conclusions: It is important to consider APBD in cases of familial dementia of unknown etiology. Ante-mortem biopsy of axillary skin may be diagnostic.

Purpose: To evaluate single photon emission computed tomographic (SPECT) imaging of regional cerebral blood flow in the diagnosis of Alzheimer disease (AD) and the differential diagnosis of the dementias., Materials and Methods: Regional cerebral blood flow SPECT was performed with inhaled xenon-133 in 261 patients and with injected technetium-99m hexamethyl-propyleneamine oxime (HMPAO) in 162 patients with possible dementia. In 16 patients, both agents were used in 1 day. SPECT images obtained in elderly healthy control subjects (with Xe-133 in 15, with Tc-99m HMPAO in 14) were available. In each patient without AD, further classification of disease was attempted. Histopathologic correlation was available in 54 patients (with autopsy in 51, with biopsy in three)., Results: SPECT diagnoses were true-positive in 37, true-negative in eight, false-positive in three, and false-negative in six patients. Sensitivity was 86% (37 of 43; 95% confidence limits = .72, .95); specificity, 73% (eight of 11; confidence limits = .39, .94); positive predictive value, 92% (37 of 40; confidence limits = .80, .98); and negative predictive value, 57% (eight of 14; confidence limits = .29, .82)., Conclusion: Regional cerebral blood flow SPECT may assist in the early and late diagnoses of AD and in the differential-diagnosis of the dementias when there is a complicated or confusing clinical picture.

Objective: To determine whether Gulf War-related illnesses are associated with central or peripheral nervous system dysfunction., Design: Nested case-control study., Participants: Twenty-three veterans with factor analysis-derived syndromes (the cases), 10 well veterans deployed to the Gulf War (the deployed controls), and 10 well veterans not deployed to the Gulf War (the nondeployed controls)., Method: With investigators blinded to group identities, participants underwent objective neurophysiological, audiovestibular, neuroradiological, neuropsychological, and blood tests., Main Outcome Measures: Evidence of neurologic dysfunction., Results: Compared with the 20 controls, the 23 cases had significantly more neuropsychological evidence of brain dysfunction on the Halstead Impairment Index (P=.01), greater interside asymmetry of the wave I to wave III interpeak latency of brain stem auditory evoked potentials (P=.02), greater interocular asymmetry of nystagmic velocity on rotational testing, increased asymmetry of saccadic velocity (P=.04), more prolonged interpeak latency of the lumbar-to-cerebral peaks on posterior tibial somatosensory evoked potentials (on right side, P=.03, and on the left side, P=.005), and diminished nystagmic velocity after caloric stimulation bilaterally (P values range from .02 to .04). Cases (n=5) with syndrome 1 ("impaired cognition") were the most impaired on brain stem auditory evoked potentials (P=.005); those (n=13) with syndrome 2 ("confusion-ataxia") were the most impaired on the Halstead Impairment Index (P=.006), rotational testing (P=.01), asymmetry of saccadic velocity (P=.03), and somatosensory evoked potentials (P< or =.01); and those (n=5) with syndrome 3 ("arthro-myo-neuropathy") were the most impaired on caloric stimulation (P< or =.01)., Conclusions: The 3 factor-derived syndromes identified among Gulf War veterans appear to represent variants of a generalized injury to the nervous system.

Purpose: To evaluate use of magnetic resonance (MR) imaging and technetium-99m pyrophosphate (PYP) scintigraphy in preoperative assessment of muscle viability after high-voltage electric injury., Materials and Methods: Twelve injured limbs were studied. Immediate, equilibrium, and delayed Tc-99m PYP scintigrams and gadolinium-enhanced and unenhanced MR images were obtained. Imaging results were compared with clinical findings., Results: Scintigraphy demonstrated nonperfusion in four limbs that were subsequently amputated, but MR imaging had poor sensitivity in nonperfused regions owing to lack of edema. Tc-99m PYP uptake increased at transition zones between normal and nonperfused regions. MR imaging allowed further characterization of these zones by demonstrating edema as enhancing (perfused) or nonenhancing (nonperfused). In all nonamputated limbs, edema showed enhancement., Conclusion: In high-voltage electric injury, gadolinium-enhanced MR imaging appears able to demonstrate zones of potential viability within radionuclide-avid tissue but has poor perfusion sensitivity when used alone.

The present study was designed to determine whether neuropsychological deficits exist in asymptomatic first-degree relatives of Alzheimer's disease (AD) patients. The neuropsychological performances of 20 first-degree asymptomatic relatives of NINCDS-ADRDA diagnosed AD patients were compared to 20 normal controls without family history of AD. Cognitive functions assessed included intelligence, memory, overall brain function, verbal learning, and language and constructional abilities. Significant statistical differences were found between the groups across several cognitive areas indicating lower functioning in the first-degree relatives of AD patients. Fifty percent of the first-degree subjects but only 20% of controls showed a pattern of significant neuropsychological deficit. The results demonstrate neuropsychological deficits in asymptomatic first-degree relatives of AD patients, suggesting that preclinical markers for AD may be present long before the clinical manifestation of the disease.

A study of 76 consecutive xenon-133 SPECT studies of regional cerebral blood flow was undertaken to determine the frequency of various patterns of blood flow in cases of clinically diagnosed probable and possible Alzheimer's disease. The reference tomographic section was a slice 6 cm above and parallel to the canthomeatal line. With the use of this technique, the "classic" finding of bilateral temporoparietal (TP) flow reductions as the sole abnormality occurred in only 28% of cases. Bilateral TP reductions accompanied by bilateral or unilateral frontal flow reductions were nearly as common (24%), and other patterns accounted for the other 48% of cases.

It is important to determine preoperatively which patients can tolerate permanent occlusion of a cervical internal carotid or cerebral artery when such a procedure may be necessary to treat cerebrovascular or neoplastic lesions. Here we report our experience in combining temporary intra-arterial balloon occlusion with concomitant cerebral blood flow imaging in preoperative evaluation of such patients. Forty-two patients with a variety of cerebrovascular and neoplastic lesions underwent trial balloon occlusion of an internal carotid or intracerebral artery. Eight patients developed both neurologic symptoms as well as brain perfusion defects during trial occlusion. Nine others developed only perfusion defects. The remainder were asymptomatic and had negative scans. Brain blood flow imaging during intra-arterial balloon occlusion identified 17 patients potentially at risk for developing postsurgical ischemic deficits. Treatment alternatives to acute arterial sacrifice were developed for these patients.

Single photon emission computed tomography (SPECT) of regional cerebral blood flow (RCBF) has been employed experimentally in the assessment of patients with dementia. The standard with which the SPECT diagnosis has been compared previously has been the initial clinical diagnosis. Recognizing that histopathologic diagnosis would be a more reliable standard, the authors compared SPECT diagnoses and clinical diagnoses with histopathologic diagnoses in a series of 18 patients who had been referred by the Alzheimer Disease Research Center. SPECT RCBF studies were carried out prospectively in 15 patients with an inhaled xenon-133 SPECT technique and in three patients with technetium-99m hexamethyl-propylene-amine oxime and triple-camera-scanner SPECT. When compared with histopathologic diagnosis, clinical diagnosis was correct in 15 of 18 patients; visual scanning diagnosis, in 13 of 18; and Xe-133-SPECT diagnosis based on quantitative ratios in regions of interest, in 14 of 15 (13 of 13 with Alzheimer disease).

Purpose: To describe the technique of using SPECT brain blood flow imaging to identify patients at risk for having strokes after balloon or surgical ligation of an internal carotid artery., Patients and Methods: 29 patients underwent temporary balloon occlusion of the internal carotid artery and blood flow imaging studies were obtained prior to sacrifice of the vessel; 11 internal carotid arteries were indeed sacrificed and form the basis of our study. Follow-up of these patients ranged from 3 to 65 days., Results: Three groups emerged: group I, patients with symptoms during occlusion and an abnormal blood flow study (one patient); group II, patients with no symptoms during the occlusion but with an unequivocally abnormal blood flow study (two patients); group III, patients without symptoms during occlusion and a normal or slightly abnormal blood flow study (eight patients)., Conclusion: Carotid sacrifice without initial and temporary balloon occlusion is unnecessarily risky. Imaging of blood flow in the brains of these patients can further improve the safety of occlusion procedures in the internal carotid artery.

Congenital generalized lipodystrophy (CGL) is a rare genetic disease characterized by the absence of body fat from birth. Focal bone lesions have also been reported, but their pathophysiology is poorly understood. To characterize skeletal abnormalities further in 3 patients with CGL, we employed whole-body radiographic skeletal surveys, magnetic resonance imaging (MRI, including gadolinium enhancement), and triple phase technetium-99m methylene diphosphonate bone scintigraphy. Radiographs showed numerous focal lesions within the long bones, as described in other reports. MRI showed that the entire marrow space of the long bones was abnormal and was characterized, at least in part, by the absence of marrow fat. Prolonged T1 and T2 times and marked gadolinium enhancement were observed in radiographically normal-appearing long bone. Radiographically lytic lesions occasionally demonstrated fluid-fluid levels on MRI and enhanced peripherally after gadolinium infusion. Bone scintigraphy findings such as periarticular hyperemia were relative subtle. We conclude that the appendicular skeleton of patients with CGL is diffusely abnormal and is predisposed to focal osteolysis and cyst formation.

Magnetic resonance (MR) imaging was used to assess for the presence of bacterial myositis, rare outside the tropics, in 13 patients with either the acquired immunodeficiency syndrome (AIDS) (n = 11) or positive results of serologic tests for the human immunodeficiency virus but without other evidence of AIDS (n = 2). Bacterial myositis was diagnosed in six patients: in five it was caused by pyogenic bacteria, and in the other, by Mycobacterium tuberculosis; in each patient, little or no subcutaneous tissue alteration occurred. On T1-weighted images in three patients, muscle abscesses showed a rim of increased signal intensity corresponding to margins between drainable pus and edematous muscle. Subcutaneous tissues appeared normal in patients with bacterial myositis but was not in the others, in whom muscle abnormalities tended to be less prominent. The latter group included patients with lymphoma (n = 1), Kaposi sarcoma (n = 2), and carbunculosis (n = 1), and three patients in whom no diagnosis was made; lymphedema was presumed to account for imaging abnormalities in four of the latter group.

Measurements of brain blood flow has evolved over the past 50 years, and during the latter half of that time radionuclide techniques have been used to study this important function. Using Xenon 133 and scintillation multiprobe systems, several teams of investigators measured regional cerebral blood flow (rCBF), and noted that under many circumstances it could be equated with local brain physiological activity. The dementias were investigated using the scintillation multiprobe method, and posterior flow deficits were described in patients who were thought to have Alzheimer's disease. The multiprobe technique gave way first to planar, and then tomographic imaging, with initial favorable results achieved by positron emission tomography (PET). Soon investigators learned to measure rCBF with single-photon emission computed tomography (SPECT) using high-sensitivity systems and 133Xe as a tracer, or high-resolution systems with 123I-iodoamphetamine (IMP), and later, 99mTc-HMPAO. Three-dimensional tomographic imaging shows to advantage the flow patterns that characterize Alzheimer's disease, with rCBF reductions in temporal, parietal, and sometimes frontal areas, as opposed to randomly distributed deficits in multiinfarct dementia, reduced frontal flow in entities such as Pick's disease, and others. Herein we will review our own experience with high-sensitivity rCBF SPECT in 119 patients with dementia, and with high-resolution SPECT, using a new, three-camera scanner and 99mTc-HMPAO in an additional 39 patients. SPECT rCBF study of patients with dementia and Alzheimer's disease, will aid in separating patients with untreatable Alzheimer's from those patients who may have treatable causes of dementia, and will be useful in evaluating experimental drugs for the treatment of Alzheimer's disease.

Regional cerebral blood flow (rCBF) was assessed in 40 chronic male schizophrenic patients (20 medicated, 20 unmedicated) and 31 matched normal controls with Dynamic Single-photon Emission Computed Tomography (D-SPECT). Blind analyses of normalized color-coded tomograms revealed significant bifrontal and bitemporal rCBF deficits in the patient group. Frontal flow deficits were most prominent in paranoid patients (n = 21) and right temporal deficits were most prominent in nonparanoid patients (n = 19). These relative regional declines were observed within the context of significantly elevated hemispheric blood flow in schizophrenics compared with controls. Reduced left frontal rCBF was associated with neuropsychological impairment on the Wisconsin Card Sorting Test and Luria-Nebraska Battery. Increased hemispheric CBF was correlated with the presence of positive schizophrenic symptoms. Medication status was unrelated to rCBF. These findings demonstrate that hypofrontality has important implications for cognitive function in some schizophrenic individuals.

Eighty-eight patients admitted to a coronary care unit with chest pain of varying etiology but without ECG evidence of an acute transmural myocardial infarction had myocardial scintigrams using technetium-99m stannour pyrophosphate (99m-Tc-PYP). Seventeen of these patients had ECG and enzymatic evidence suggestive of acute subendocardial myocardial infarction. In each of these the scintigrams were postivie demonstrating increased 99m-Tc-PYP uptake either in a faintly but diffusely positive pattern or in a well-localized strongly positive one. The remaining 71 patients did not evolve ECG or enzymatic evidence of acute myocardial infarction. In each of these patients the myocardial scintigram was negative. Thus 99m-Tc-PYP myocardial scintigrams are capable of identifying the presence of acute subendocardial myocardial infarction in patients. The absolute frequency with shich subendocardial myocardial infarction can be recognized utilizing this technique will have to be established in a larger number of patients in the future.

In 17 dogs with acute myocardial infarcts produced by ligation of the proximal left anterior descending coronary artery, a comparative study was made of myocardial scintigrams obtained with technetium-99m stannous pyrophosphate (99mTc-PYP) and thallium-201 (201T1), tissue levels of 99mTc-PYP and 201T1 uptake, histopathologic alterations, and regional myocardial perfusion measured with radioactive microspheres. 9 of the 10 hearts examined histologically had transmural infarcts with outer peripheral, inner peripheral, and central zones characterized by distinctive histopathologic features. A progressive reduction in myocardial blood flow was demonstrated between normal myocardium and the centers of the infarcts, and correlated well with progressive reduction in 201T1 upatke in the same regions. Marked 99mTc-PYP concentration occurred in areas with partial to homogeneous myocardial necrosis and residual perfusion located in the outer peripheral regions of the infarcts. The latter areas also were characterized by the presence of muscle cell calcification. The patterns of distribution of 99mTc-PYP and 201T1 explained the filling defects on 201T1 myocardial scintigrams and the doughnut patterns on 99mTc-PYP myocardial scintigrams in dogs with transmural infarcts. One dog with a subendocardial infarct had a small homogeneous area of activity on the 99mTc-PYP myocardial scintigram, and showed marked uptake of 99mTc-PYP in subendocardial areas of extensive necrosis and calcification still receiving some coronary perfusion. Thus, the data indicate that the status of regional myocardial perfusion is a key determinant for the occurrence of distinctive patterns of myocardial necrosis and for the scintigraphic detection of acute myocardial infarcts with 99mTc-PYP and 201T1.

Regional CBF (rCBF) was measured quantitatively using the inert-gas washout technique with xenon-133 and single-photon emission computed tomography. Tomographic data were reconstructed by filtered back projection, and flow was calculated according to the double-integral method. Ninety-seven subjects ranging in age from 20 to 59 years received a single examination; eight of these received a second examination within 1 h of the first; seven others received a second examination separated from the first by 1-10 days. Transverse-section images were obtained at 2, 6, and 10 cm above and parallel to the canthomeatal line (CML). Cortical gray matter flows were obtained from 12 brain regions in the slice 6 cm above the CML, and cerebellar and inferior cerebral gray matter flows were obtained from 4 regions in the slice 2 cm above the CML. Mean gray matter flow was 72 +/- 12 ml/min/100 g, with highest flows in the parietal lobes and visual cortex. No significant differences in rCBF occurred when a second study followed the first by 30 min to 10 days. Right-sided rCBF was slightly higher than left in all regions except frontal and parietal lobes where there was no difference. Flow was higher in women than in men and declined mildly with age for both sexes (slope = -0.33 ml/min/100 g/year; p less than 0.05).

Myocardial scinitgrams, using 99mTc-stannous pyrophosphate, showed an acute posterior infarction and an abnormally placed left kidney in a 24-year-old hypertensive man; Further study revealed that the kidney was displaced by a mass later proven to be a pheochromocytoma. The latter was the cause of his hypertension and probably instigated the acute myocardial infarction.

Technetium-99m-phosphate imaging is particularly valuable in detecting (1) small transmural infarcts (3 g and larger in size); (2) new acute transmural infarcts in or near regions of old infarction; (3) acute subendocardial infarcts (larger than 3 g in size); (4) acute infarction in patients with left bundle branch block; and (5) perioperative myocardial infarction. Localization of inferior and posterior myocardial infarction is improved with imaging. Sizing of acute anterior and lateral infarcts has been accurately done in dogs and should prove helpful in patients. Extensive evaluation in both experimental animals and in patients has shown 99mTc-phosphate myocardial imaging to be a useful clinical tool, and it may be one of the most sensitive noninvasive ways presently available to identify acute myocardial necrosis. It is important to understand that 99mTc-phosphate imaging has a different pathophysiology basis from EKG's or serum enzymes. These tests do not compete but instead should complement one another.

Dynamic single-photon emission computed axial tomography (CAT) with inhaled xenon-133 was used to measure regional cerebral blood flow in 10 drug-free patients with DSM-III-diagnosed panic disorder and in five normal control subjects. All subjects underwent regional cerebral blood flow studies while at rest or during normal saline infusion and during sodium lactate infusion. Six of the 10 patients and none of the control subjects experienced lactate-induced panic attacks. Lactate infusion markedly raised hemispheric blood flow levels in both control subjects and patients who did not panic. Patients who did panic experienced either a minimal increase or a decrease in hemispheric blood flow.

Attenuation of photons in single-photon emission tomography (SPECT) makes three-dimensional reconstruction of unknown radioactivity distributions a mathematically intractable problem. Approaches to approximate SPECT reconstruction range from ignoring the effect of photon attenuation to incorporating assumed attenuation coefficients into an iterative reconstruction procedure. We have developed a computer-based simulation method to assess the relative effectiveness of attenuation compensation procedures. The method was used to study four procedures for myocardial SPECT using an infarct-avid radiopharmaceutical, Tc-99m stannous pyrophosphate. Reconstructions were evaluated by two criteria: overall (sum-of-squares) accuracy, and accuracy of lesion sizing. For moderate- to high-contrast studies there were no significant differences among the reconstructions by either evaluation criterion; for low contrast ratios the iterative method produced lower sum-of-squares criterion; for low contrast ratios the iterative method produced lower sum-of-squares error. We conclude that the additional expense of the iterative method is not justified under the conditions of this study. The approach used here is a convenient tool for evaluating specific SPECT reconstruction alternatives.

A four-pinhole longitudinal tomographic system, with collimator and software, was developed for a standard-field portable scintillation camera. This system was used with technetium--99m pyrophosphate (Tc-PPi) to quantify the volume of infarcted myocardium in 27 dogs with experimental myocardial infarcts. These were induced by ligation of the left anterior descending (LAD) or the circumflex coronary artery. Tomographic estimations of scintigraphic infarct size agreed well with postmortem findings when the circumflex group (r = 0.87) and LAD group (r = 0.83) were considered separately, but the correlation fell when the groups were pooled (r = 0.73). Whereas multipinhole tomography extends Tc-PPi infarct sizing capability in animals to include posterior and subendocardial infarcts as well as anterior lesions, the tomographic sections contain enough blur artifacts to lower the sizing accuracy of the method. The main advantage of the technique may well be its ability to aid in detection and location of small myocardial infarcts.

99mTc-PYP myocardial scintigrams represent a means to detect and localize acute myocardial necrosis. These scintigrams are expected to be abnormal with acute myocardial infarcts of at least 3 grams in weight if serial imaging is utilized and proper attention to technique is provided. Any etiology of myocardial necrosis may produce abnormal 99mTc-PYP scintigrams if the damage is relatively localized and includes at least 3 grams of tissue. It is possible to accurately size acute anterior and anterolateral transmural myocardial infarcts using area or 2 dimensional measurements. Further development in imaging cameras and computer techniques allowing three dimensional reconstruction of myocardial infarcts with this and similar imaging techniques may allow relatively precise quantitation of other types of myocardial infarcts. The "doughnut" and "persistently abnormal" 99mTc-PYP scintigrams appear to have anatomic and prognostic significance at least in subsets of patients studied, but larger numbers of individuals need to be evaluated before final conclusions regarding their ultimate prognostic significance can be reached.

To obtain insight into the mechanism(s) responsible for the direct visualization of acute myocardial infarcts by myocardial scintigraphy with technetium-99m stannous pyrophosphate (99mTc-PYP), scintigraphic and morphologic studies were performed in 22 dogs subjected to occlusion of the proximal left anterior descending coronary artery (LAD). Grossly visible myocardial infarcts occurred in ten of 11 dogs with LAD occlusion for one day, five with LAD occlusion for two days, two with LAD occlusion for seven days and two with LAD occlusion for 13 days. Rare, microscopic foci of necrosis were observed in one dog with LAD occlusion for one day, and no lesions were present in two dogs subjected to temporary LAD occlusion for eight minutes and reflow for 24 hours. In the latter three dogs, 99mTc-PYP myocardial scintigrams were negative. In the 19 dogs with gross infarcts, 99mTc-PYP myocardial scintigrams were strongly positive at one and two days after LAD occlusion, much less positive at seven days and faintly positive at 13 days after occlusion. Positive myocardial scintigrams in most showed "doughnut" patterns, with marked peripheral concentration of radioactivity around central zones of much lower activity. On histologic examination, the one and two-day-old infarcts exhibited subendocardially located central zones and surrounding peripheral zones, both of which showed distinctive histopathological and histochemical features, including the selective occurrence in the peripheral zones of calcified muscle cells with ultrastructurally demonstrable apatite-like crystals in mitochondria. Selective occurrence of high tissue levels of 99mTc-PYP radioactivity also was demonstrated in the peripheral zones of four infarcts. Hearts with older infarcts (seven and 13 days) showed progressive replacement of necrotic myocardium by granulation tissue and progressive reduction in calcium deposits in the areas of damage. The data obtained in this study establish a temporal and topographical relationship between calcium accumulation in acute myocardial infarcts and 99mTc-PYP uptake responsible for scintigraphic detection of the lesions with this radionuclide in dogs subjected to proximal LAD occlusion.

The topographic relationship between the uptake of technetium-99m pyrophosphate (PPi) and myocardial infarction delineated by 2,3,5-triphenyl tetrazolium chloride (TTC) was studied in a canine model of permanent coronary occlusion (24-48 hr). Photographs of TTC staining and scintigraphic images of PPi uptake were planimetered for infarct area. In addition, narrow tissue samples (3 X 10 mm) were taken on both sides of the TTC border and counted for PPi uptake. A significant correlation (p less than 0.001) was found between area of PPi uptake and area of myocardium unstained by TTC (r = 0.84 in epicardium and r = 0.91 in endocardium). The slope relating PPi to TTC for all infarcts was 1.01 +/- 0.11, indicating that variations in infarct size were followed equally by the two techniques. Tissue counting showed the ratio of PPi activity just inside the infarct to activity just outside the infarct to be 9.2 +/- 0.6 (mean +/- s.e.m.). Thus, PPi is distributed topographically in a manner identical to the distribution of irreversibly injured myocardium as delineated by TTC.

We have developed a method by which any two sets of R-wave-synchronized radionuclide images may be registered, color-coded, and displayed in cinematic fashion so that the image sets are superimposed and shown simultaneously in contrasting colors. The technique has been applied to technetium-99m stannous pyrophosphate (Tc-99m PPi) and equilibrium blood-pool images. Gated Tc-99m PPi and gated blood-pool image sets (16 frames per cardiac cycle) were acquired in identical projections. Image sets were then registered, if necessary, and color-coded by a computer algorithm. Our initial experience suggests that this overlay technique may be of value to: (a) detect right ventricular infarction with greater precision; (b) provide a better estimate of anatomic location and circumferential extent of Tc-99m PPi myocardial uptake relative to the ventricular blood pool; and (c) distinguish between segmental contraction abnormalities caused by recent infarction (identified by abnormal Tc-99m PPi uptake) and segmental contraction abnormalities caused by ischemia or previous myocardial infarction.

Myocardial infarct size was estimated by three methods in a canine model, using Tc-99m pyrophosphate at 24 and 48 hr after coronary ligation. A gamma camera provided anterior, LAO, and lateral views, and was then fitted with multipinhole (MPH) and rotating-slanthole (RSH) collimators for tomographic studies, processed by computer to display frontal sections of the chest. Infarct weight was measured postmortem for comparison. All transmural infarcts were detected by all three imaging techniques. RSH tomography was superior to both MPH tomography and planar imaging for the detection of nontransmural infarction. Infarcts as small as 1.0 g were detected. Estimates of infarct volume measured from RSH slices showed an excellent correlation with infarct weight (r = 0.89) and were reproducible within acceptable limits. Estimates on infarct volume measured from MPH slices demonstrated a significantly poorer correlation with infarct weight (r = 0.48, p less than 0.01). Both tomographic techniques may improve infarct visualization by suppressing overlying activity and increasing contrast between infarct and background, but both produce significant blur artifacts that hamper their utilization by inexperienced observers.