The FDG/PET methodology for early detection of disease onset: a statistical model.

The development of appropriate statistical methodologies for neuroimaging studies is dependent upon the research question of interest. Often studies are analyzed with techniques that may not be appropriate for the research question but are accepted owing to convention, familiarity, or apparent statistical sophistication. Neuroimaging data are particularly complex owing to (a) the high number of potential dependent variables (i.e., regions of interest) coupled with the practical limitations on sample size; (b) the known physical properties of scanners (e.g., resolution) interacting with the intricate and variable structure of the human brain; and (c) mathematical properties introduced into the data by the physiological model for quantification. In this article, a statistical model will be discussed for addressing a particular problem in clinical studies. Given that there is a characteristic abnormality in regional glucose metabolism in a specific disease, can a probabilistic statement be made with confidence regarding the likelihood of an individual scan being similar to those from the disease group or normal subjects? The model capitalizes on known statistical aspects of normal regional glucose metabolism. To illustrate the model, data will be presented on normal subjects, patients with confirmed Huntington's disease, and subjects at risk for the disease. Reliability and clinical validity of the model will be discussed.

The combined use of positron emission tomography and DNA polymorphisms for preclinical detection of Huntington's disease.

Twenty-three persons at risk for Huntington's disease (HD) have been studied using a polymorphic human linked DNA marker (D4S10) and positron emission tomography (PET). We determined the likelihood of inheritance of the gene for HD in 13 persons, using DNA polymorphism studies. Of these, eight persons had a greater than 90% probability of being presymptomatic heterozygotes for HD. Three of these eight subjects had caudate glucose utilization detected by PET that was more than 2 standard deviations (SD) below the age-matched control mean. Measurement of caudate glucose utilization in the other five presumed presymptomatic heterozygotes revealed results between 1 and 2 SD below the mean. Five persons had a less than 10% likelihood of having inherited the abnormal gene for HD. Of these, four had normal rates of glucose utilization in the caudate nuclei. However, one individual with DNA results indicating a low risk of developing HD had abnormally low measures of caudate glucose utilization. This suggests that a recombination had occurred between the linked marker and the gene in this person. These studies suggest that PET studies of caudate glucose utilization may help to confirm results of DNA studies in some persons, and may provide an opportunity to detect when DNA results may be incorrect due to recombination.

Cortical glucose metabolism in Huntington's disease.

We measured cortical glucose metabolism with positron emission tomography in 39 patients with Huntington's disease (HD) and in 34 controls. In the 23 patients with symptoms for less than 5 years, there was a 15% decrease in metabolism in frontal and inferior parietal cortex. In 16 patients with symptoms for more than 5 years, all cortical areas (except temporal) were significantly involved, with metabolic rates 25 to 30% below those of controls. These data indicate the presence of a diffuse abnormality of cortical function with early involvement of frontal lobes in HD, suggesting that the clinical manifestations may not be related solely to basal ganglia pathology, even in early disease.

Positron emission tomography in the early diagnosis of Huntington's disease.

We studied 10 patients with early Huntington's disease and 7 normal age-matched controls with positron emission tomography (PET) using fluorodeoxyglucose. Subjects had little or no caudate nucleus atrophy and had not received any medications. The results demonstrated that hypometabolism of glucose preceded tissue loss. Furthermore, patients with minimal neurologic or psychiatric symptoms and no obvious CT changes may be differentiated from normal persons with high accuracy by PET. PET is helpful in the early diagnosis of Huntington's disease irrespective of the mode of presentation. PET may also be useful for preclinical detection and may supplement information from DNA studies.

PET studies of cerebral glucose metabolism in idiopathic torticollis.

Regional cerebral glucose metabolism was studied in 16 patients with idiopathic torticollis, using positron emission tomography. Analysis of subcortical regions revealed no consistent focal abnormality of cerebral metabolic rate for glucose, but there was a bilateral breakdown of the normal relationships between the thalamus and basal ganglia. The findings suggest disruption of the pallidothalamic projections in this focal dystonia and may imply a disturbance of GABA.

Reduced glucose metabolism in the frontal cortex and basal ganglia of multiple sclerosis patients with fatigue: a 18F-fluorodeoxyglucose positron emission tomography study.

To investigate the pathophysiology of fatigue in MS, we assessed cerebral glucose metabolism (CMR-Glu) in 47 MS patients using PET and 18F-fluorodeoxyglucose. Applying the Fatigue Severity Scale (FSS), we first compared MS patients with severe fatigue (MS-FAT, n = 19, FSS > 4.9) and MS patients without fatigue (MS-NOF, n = 16, FSS < 3.7) on a pixel-by-pixel basis using Statistical Parametric Mapping (SPM95). Second, we compared FSS values of all 47 patients covering the whole range of this scale with CMRGlu using an analysis of covariance (SPM95). In addition, we determined global CMRGlu by region-of-interest analysis. Sixteen healthy subjects served as control subjects (CON). Global CMRGlu was significantly lower in both MS groups compared with CON (CON 43.3 +/- 6.9 mumol/100 mL/min, MS-FAT 34.7 +/- 4.4, MS-NOF 35.4 +/- 4.5) but was not related to fatigue severity. Comparing the two MS groups, SPM95 analysis revealed predominant CMRGlu reductions bilaterally in a prefrontal area involving the lateral and medial prefrontal cortex and adjacent white matter, in the premotor cortex, putamen, and in the right supplementary motor area of MS-FAT. In addition, there were CMRGlu reductions in the white matter extending from the rostral putamen toward the lateral head of the caudate nucleus. FSS values were inversely related to CMRGlu in the right prefrontal cortex. CMRGlu in the cerebellar vermis and anterior cingulate was relatively higher in MS-FAT than in MS-NOF patients. CMRGlu of both regions showed positive correlations with FSS values. Our data suggest that fatigue in MS is associated with frontal cortex and basal ganglia dysfunction that could result from demyelination of the frontal white matter.

A method for comparing different procedures of estimating regional glucose metabolism using fluorine-18-fluorodeoxyglucose.

The purpose of this paper is to describe a method for determining whether a particular procedure for estimating regional metabolism using the deoxyglucose tracer analogue yields better data than another in terms of subsequent statistical analysis. The method is based on a simple model of regional cerebral glucose metabolism with three potential sources of metabolic variability, namely individual differences in cerebral metabolic rate, consistent regional differences and error. When the literature rate constants were compared to a dynamic procedure for estimating regional rate constants in patients with Huntington's Disease, the literature values were clearly superior in that the error component was approximately half (18.5 versus 39.3%). Although these results cannot be generalized to all procedures for estimating regional glucose metabolism, the method can be applied to determine if a particular procedure will be more sensitive than another to differences between groups.

The role of bone scintigraphy in the evaluation of talar dome fractures.

We undertook a retrospective study of 122 patients with ankle pain to determine the accuracy of bone scintigraphy using 99mTc-methylene diphosphonate (MDP) for detection of osteochondral talar dome fractures (OCTDF). Plain radiographs, which were available in 97 patients, had not revealed any abnormality in the talar dome. Bone scintigraphy was followed by CT, which was considered to be the reference test in diagnosing OCTDF. Analysis of our data showed that when the bone scan findings in the two highest confidence categories (high and moderate probability) were accepted as abnormal, the sensitivity and the specificity of the test were 0.94 and 0.76, respectively. Although CT is mandatory to establish the stage of OCTDF, it cannot be used routinely due to its high cost. Bone scintigraphy appears to be a good screening procedure that will identify patients who are likely to benefit from further radiographic studies such as CT. These findings are subject to further confirmation in a prospective study.

Renal trauma.

Renal injuries are classified as minor, major, and critical/catastrophic for purposes of management. The radionuclide renal scintigram is a safe, simple, and extremely sensitive means of establishing the presence of an injury and monitoring kidney function during conservative management, which is utilized in the vast majority of cases. The information that may be obtained from radionuclide imaging is the state of overall and regional blood transit, overall and regional parenchymal function, and urinary extravasation.

Cardiovascular adaptations in Andean natives after 6 wk of exposure to sea level.

Six male Quechua Indians (34.0 +/- 1.1 yr, 159.5 +/- 2.1 cm, 60.5 +/- 1.6 kg), life-long residents of La Raya, Peru (4,350-m altitude with an average barometric pressure of 460 Torr), were studied using noninvasive methods to determine the structural and functional changes in the cardiovascular system in response to a 6-wk deacclimation period at sea level. Cardiac output, stroke volume, and left ventricular ejection fractions were determined using radionuclide angiographic techniques at rest and during exercise on a cycle ergometer at 40, 60, and 90% of a previously determined maximal O2 consumption. Subjects at rest were subjected to two-dimensional and M-mode echocardiograms and a standard 12-lead electrocardiogram. Hemoglobin and hematocrit were measured on arrival at sea level by use of a Coulter Stacker S+ analyzer. After a 6-wk deacclimation period, all variables were remeasured using the identical methodology. Hemoglobin values decreased significantly over the deacclimation period (15.7 +/- 1.1 to 13.5 +/- 1.2 g/dl; P less than 0.01). The results indicate that the removal of these high-altitude-adapted natives from 4,300 m to sea level for 6 wk results in only minor changes to the cardiac structure and function as measured by these noninvasive techniques.

Osteitis pubis in athletes. Infection, inflammation or injury?

Medical records of 59 patients (9 females and 50 males), who presented to sports medicine clinics at the Australian Institute of Sport and the University of British Columbia between 1985 and 1990 and who were diagnosed as suffering osteitis pubis, were reviewed and comparison of data obtained was made with the literature. Women average 35.5 years of age (30 to 59 years) and men 30.3 years (13 to 61 years). Sports most frequently involved were running, soccer, ice hockey and tennis. Clinical presentations of osteitis pubis fell into 4 main groups. 'Mechanical' (sport-related) was the largest group (n = 48), followed by 'obstetric' (n = 5), 'inflammatory' (n = 4) and 'other' (n = 2). Period of follow-up averaged 10.3 months (1 to 20 months) in women and 17.5 months (2 to 96 months) in men. Full recovery, when documented, averaged 9.5 months in men and 7.0 months in women. Osteitis pubis recurred in 25% of these men and none of these women at follow-up. The most frequent symptoms were pubic pain and adductor pain. Men also presented with lower abdominal, hip and perineal or scrotal pain; women with hip pain. Most common signs were tenderness of the pubic symphysis and tenderness of adductor longus muscle origin. Men also revealed tenderness of one or both the superior pubic rami and evidence of decreased hip rotation (unilateral or bilateral). Evidence of pelvic malalignment and/or sacroiliac dysfunction was frequently seen in both men and women. There was poor correlation between radiographic and isotope bone scan findings and the site and duration of symptoms and signs. Femoral head ratios were estimated on 30 hips in the series and 2 were judged to be at the upper limit of normal, perhaps indicating a form of epiphysiolysis producing tilt deformity of the head of the femur. It is clear that osteitis pubis in athletes is not uncommon and that factors such as loss of rotation of hips and previous obstetric history are important in the aetiology and management of this condition. Pelvic infection, which was believed to be the primary factor of osteitis pubis in the literature up until the 1970s, plays a very small role in this condition in athletes.

Single photon emission computed tomography using 99mTc-HM-PAO in the routine evaluation of Alzheimer's disease.

Regional cerebral blood flow was studied in 7 patients with clinically suspected Alzheimer's disease and 10 normal controls by single photon computed emission tomography (SPECT) using HM-PAO. All patients with Alzheimer's disease and no controls had parietal lobe hypoperfusion which was usually bilateral. In patients with more severe dementia hypoperfusion extended into the frontal lobes. Parietal lobe hypoperfusion corresponds to parietal lobe degeneration which is the one of the first neocortical regions to show the typical degenerative changes of Alzheimer's disease. SPECT with HM-PAO is a non-invasive investigation available in most nuclear medicine departments and complements existing tests in the routine evaluation of patients presenting with dementia.

Subacute splenic abscess. Appearance on indium-111 leukocyte, gallium-67, and technetium-99m sulfur colloid imaging.

A case of a 23-year-old man with an encapsulated, anaerobic splenic abscess is reported. Both the In-111 leukocyte and Tc-99m sulfur colloid scans demonstrated an intrasplenic defect. The Ga-67 citrate scan revealed uptake in the rim of the abscess only where the abscess cavity was relatively photon-deficient. The combined Tc-99m sulfur colloid/In-111 leukocyte/Ga-67 scan appearance of a subacute splenic abscess has not been described previously. In cases suspected to be splenic abscesses the combined In-111 leukocyte/Tc-99m sulfur colloid imaging is the most useful.

Isolated fractures of the capitate: use of nuclear medicine as an aid to diagnosis.

Fractures of the capitate are considered to be uncommon injuries of the wrist, however, delay in diagnosis may result in prolonged disability and avascular necrosis. Two cases are reported in which an isolated fracture of the capitate was diagnosed with a 99mTc-MDP nuclear medicine bone scan and confirmed with CT scan or repeated conventional x-rays. These two cases illustrate that an isolated fracture of the capitate should be considered in an individual presenting with persistent wrist pain of traumatic origin, even when conventional x-ray views are negative. The nuclear medicine bone scan can be a useful investigative tool and serve to guide further radiological investigations.

Femoral stress abnormalities: improved scintigraphic detection with frog-leg view.

To identify a better scintigraphic imaging technique for detecting proximal femoral stress abnormalities, 51 consecutive patients with hip pain and the clinical suspicion of stress injury underwent three-phase bone scanning with technetium-99m methylene diphosphonate. Delayed scanning included anterior and frog-leg views of the hips. Fifteen patients had focal stress abnormalities of the femoral neck or lesser trochanter; all were detected with the frog-leg view, but only seven were detected with the standard anterior view. Stress abnormalities involving the lesser trochanter were depicted especially well on the frog-leg view.

Central adaptations in aerobic circuit versus walking/jogging trained cardiac patients.

This study was done to determine (a) whether in coronary artery disease (CAD) left ventricular (LV) adaptations differed after 6 months of walking/jogging (legs-only, LO) versus aerobic circuit training (arms and legs, AL) versus a control group, and (b) whether a transfer of fitness to the untrained arms in the LO group was related to superior LV adaptations. Peak oxygen uptake for arm and leg ergometry and for cycle ergometry using radionuclide cardiac angiography were performed before and after training. Leg and arm VO2peak increased significantly by 13% in the AL group, and by 13% and 7%, respectively, for the LO group. LV function was greater after training for the LO versus the AL group. Improvements in systolic and diastolic function and a speculated hypervolemia explain these LV adaptations. In CAD patients, walking/jogging produces greater LV function improvements versus circuit training, possibly due to differences in the exercised muscle mass.