Choroid Plexus Calcification Correlates with Cortical Microglial Activation in Humans: A Multimodal PET, CT, MRI Study.

BACKGROUND AND PURPOSE: The choroid plexus (CP) within the brain ventricles is well-known to produce cerebrospinal fluid (CSF). Recently, the CP has been recognized as critical in modulating inflammation. MRI-measured CP enlargement has been reported in neuroinflammatory disorders like MS as well as with aging and neurodegeneration. The basis of MRI-measured CP enlargement is unknown. On the basis of tissue studies demonstrating CP calcification as a common pathology associated with aging and disease, we hypothesized that previously unmeasured CP calcification contributes to MRI-measured CP volume and may be more specifically associated with neuroinflammation. MATERIALS AND METHODS: We analyzed 60 subjects (43 healthy controls and 17 subjects with Parkinson's disease) who underwent PET/CT using 11C-PK11195, a radiotracer sensitive to the translocator protein expressed by activated microglia. Cortical inflammation was quantified as nondisplaceable binding potential. Choroid plexus calcium was measured via manual tracing on low-dose CT acquired with PET and automatically using a new CT/MRI method. Linear regression assessed the contribution of choroid plexus calcium, age, diagnosis, sex, overall volume of the choroid plexus, and ventricle volume to cortical inflammation. RESULTS: Fully automated choroid plexus calcium quantification was accurate (intraclass correlation coefficient with manual tracing = .98). Subject age and choroid plexus calcium were the only significant predictors of neuroinflammation. CONCLUSIONS: Choroid plexus calcification can be accurately and automatically quantified using low-dose CT and MRI. Choroid plexus calcification-but not choroid plexus volume-predicted cortical inflammation. Previously unmeasured choroid plexus calcium may explain recent reports of choroid plexus enlargement in human inflammatory and other diseases. Choroid plexus calcification may be a specific and relatively easily acquired biomarker for neuroinflammation and choroid plexus pathology in humans.

Change in lung tumor volume as a biomarker of treatment response: a critical review of the evidence.

SPECIFIC AIM: To review the evidence indicating that volumetric image analysis of computed tomography scans meets specifications for qualification as a biomarker in clinical trials or the management of individual patients with lung cancer. METHODS: Claims of value were broken down into questions about technical feasibility, accuracy, the precision of measurement, sensitivity, the correlations with health outcomes, and the risks of producing misleading information. For each claim, the pertinent literature was reviewed. RESULTS: Technical feasibility has now been shown, but only in limited contexts. Accuracy has been demonstrated, but only for tumors with favorable anatomical features. Measurement error still makes the assessment of change in small nodules precarious in diagnostic settings unless rigorous image acquisition and analysis procedures are followed. Precision is sufficient in some larger masses to make volumetrics a sensitive biomarker. In a few trials, correlations with clinical outcomes have been higher for volumetric-based measures than for unidimensional or bidimensional diameters. Value in clinical practice settings and clinical trials has been suggested, but not proven. CONCLUSION: The weight of the evidence indicates there are circumstances in which volumetric image analysis adds value to clinical trial science and the practice of medicine.

Data sets for the qualification of volumetric CT as a quantitative imaging biomarker in lung cancer.

The drug development industry is faced with increasing costs and decreasing success rates. New ways to understand biology as well as the increasing interest in personalized treatments for smaller patient segments requires new capabilities for the rapid assessment of treatment responses. Deployment of qualified imaging biomarkers lags apparent technology capabilities. The lack of consensus methods and qualification evidence needed for large-scale multi-center trials, as well as the standardization that allows them, are widely acknowledged to be the limiting factors. The current fragmentation in imaging vendor offerings, coupled with the independent activities of individual biopharmaceutical companies and their contract research organizations (CROs), may stand in the way of the greater opportunity were these efforts to be drawn together. A preliminary report, "Volumetric CT: a potential biomarker of response," of the Quantitative Imaging Biomarkers Alliance (QIBA) activity was presented at the Medical Imaging Continuum: Path Forward for Advancing the Uses of Medical Imaging in the Development of New Biopharmaceutical Products meeting of the Extended Pharmaceutical Research and Manufacturers of America (PhRMA) Imaging Group sponsored by the Drug Information Agency (DIA) in October 2008. The clinical context in Lung Cancer and a methodology for approaching the qualification of volumetric CT as a biomarker has since been reported [Acad. Radiol. 17, 100-106, 107-115 (2010)]. This report reviews the effort to collect and utilize publicly available data sets to provide a transparent environment in which to pursue the qualification activities in such a way as to allow independent peer review and verification of results. This article focuses specifically on our role as stewards of image sets for developing new tools.

Sex differences in regional cerebral glucose metabolism during a resting state.

Positron emission tomography was used to evaluate the regional distribution of cerebral glucose metabolism in 61 healthy adults at rest. Although the profile of metabolic activity was similar for men and women, some sex differences and hemispheric asymmetries were detectable. Men had relatively higher metabolism than women in temporal-limbic regions and cerebellum and relatively lower metabolism in cingulate regions. In both sexes, metabolism was relatively higher in left association cortices and the cingulate region and in right ventro-temporal limbic regions and their projections. These results are consistent with the hypothesis that differences in cognitive and emotional processing have biological substrates.

Neuropsychological function in schizophrenia. Selective impairment in memory and learning.

Unmedicated schizophrenic patients (according to DSM-III-R criteria) (n = 36) and age-matched normal controls (n = 36), balanced for parental socioeconomic status, were administered a battery of standardized neuropsychological tests. Patients showed generalized impairment relative to controls and a selective deficit in memory and learning compared with other functions. Selective impairment was not found on tests related to frontal system function (abstraction, verbal fluency, and motor). The observed pattern is consistent with greater involvement of the temporal-hippocampal system, against the background of diffuse dysfunction. Although impairment in memory and learning has been reported, the selectivity and relative severity compared with other behavioral functions have not been recognized. The specificity of this profile merits further examination. These findings lend support to the hypothesized importance of the temporal-hippocampal region in understanding the pathophysiology of schizophrenia.

Magnetic resonance imaging in schizophrenia. I. Volumetric analysis of brain and cerebrospinal fluid.

The study reports magnetic resonance imaging data for 42 patients with schizophrenia and 43 normal controls. Volumetric measures were obtained with a validated computerized algorithm for segmentation of cranial volume into brain tissue and central and peripheral cerebrospinal fluid (CSF), with high inter-operator reliability. Patients did not differ significantly in whole-brain volume, but had higher whole-brain CSF volume and higher ratios of ventricular and sulcal CSF to cranial volume. Covarying age and education did not affect the differences. However, there was considerable overlap both in CSF volumes and in volume-cranium ratios, and most patients were within the normal range. This suggests that anatomic changes reflected in CSF can provide a limited substrate for schizophrenia and may apply only to subpopulations. Although there was no gender x diagnosis interaction, the results for sulcal CSF were significant only for men, whereas for women, the ventricular ratios were marginally higher in patients.

Volunteers for biomedical research. Recruitment and screening of normal controls.

We examined the process of accruing healthy control subjects for biomedical research on brain function. Of 1670 responders to newspaper advertising, 23.1% were uninterested when learning more about the studies, and 50.9% of those remaining were found by structured telephone screening to meet exclusionary criteria for having a history of psychiatric, neurologic, or medical disease that might affect brain function. Of 312 volunteers passing the telephone screening who came to an in-person evaluation by a physician and agreed to participate, 49.7% were found to meet exclusionary criteria, and only 157 were admitted to the study. This underscores the importance of attending to the issue of screening and assessment of "normal volunteers." Alternative strategies should be considered for enriching the pool.

Resting cerebral glucose metabolism in first-episode and previously treated patients with schizophrenia relates to clinical features.

BACKGROUND: Functional neuroimaging can elucidate brain dysfunction in schizophrenia. The frontal, temporolimbic, and diencephalic regions have been implicated. There is a lack of prospective samples of first-episode and previously treated patients followed up longitudinally. METHODS: Patients and controls (42 per group) were studied. Positron emission tomography with flurodeoxyglucose, cross-registered with magnetic resonance imaging, measured metabolism. Scales assessed clinical features, premorbid adjustment, and outcome. RESULTS: There were no differences between groups in whole-brain metabolism or regional ratios or in anterior-posterior gradients, but left midtemporal metabolism was relatively higher in patients. This was pronounced in the negative and Schneiderian and absent in the paranoid subtypes. Higher metabolism and lower relative left hemispheric values were associated with better premorbid adjustment and outcome. A higher subcortical-cortical gradient was noted in first-episode patients. CONCLUSIONS: There are no resting metabolic abnormalities in any brain region, but abnormal gradients are evident. These vary in subtypes, and laterality is associated with functioning. The results support the hypothesis of temporolimbic disturbance in schizophrenia that is all ready present at the onset of illness.

Relationships between verbal memory performance and the cerebral distribution of fluorodeoxyglucose in patients with schizophrenia.

Quantitative resting fluorodeoxyglucose-positron emission tomography scans were performed on 42 patients with schizophrenia. Magnetic resonance imaging-based regions of interest were transposed onto the corresponding positron emission tomography images. Region to whole brain ratios were calculated from the mean regional activity per pixel across both hemispheres (left plus right). Laterality scores were calculated from the difference between the mean activity in homotopic regions of the two hemispheres (left minus right). Subjects were tested contemporaneously with the Logical Memory subtest of the Wechsler Memory Scale. The subtest was scored with modified criteria to provide information about verbal recall, perseverations, and other components of verbal memory. Deficits in recall were associated with increased metabolism in selected regions of the left hemisphere that are known to mediate aspects of verbal memory. The findings support hypotheses suggesting that the left hemisphere is functionally overactive in schizophrenia.

Subcortical MRI volumes in neuroleptic-naive and treated patients with schizophrenia.

OBJECTIVE: This study examined whether subcortical volumes of the basal ganglia and thalamus in schizophrenic patients are related to neuroleptic exposure and symptom severity. METHOD: Basal ganglia substructures and thalamic volumes were measured with magnetic resonance imaging in 96 patients with schizophrenia (50 men and 46 women) and 128 healthy comparison subjects (60 men and 68 women). Twenty-one of the patients were neuroleptic-naive; of the 75 previously treated patients, 48 had received typical neuroleptics only, and 27 had received typical and atypical neuroleptics. The relation of volume measures to treatment status, exposure to neuroleptics, and symptoms was examined. RESULTS: The neuroleptic-naive patients did not differ from the healthy comparison subjects in subcortical volumes except for lower thalamic volume. In the neuroleptic-naive group, volumes did not correlate with severity of negative symptoms, but higher volumes in both the thalamus and the putamen were associated with more severe positive symptoms. The previously treated group showed higher volumes in the putamen and globus pallidus than the healthy comparison subjects and the neuroleptic-naive patients. In the treated group, a higher dose of a typical neuroleptic was associated with higher caudate, putamen, and thalamus volumes, whereas a higher dose of an atypical neuroleptic was associated only with higher thalamic volume. Higher subcortical volumes were mildly associated with greater severity of both negative and positive symptoms. CONCLUSIONS: Increased subcortical volumes in treated schizophrenic patients seem to be medication-induced hypertrophy. This hypertrophy could reflect structural adaptation to receptor blockade and may moderate the effects of neuroleptic treatment.

Limbic activation during cue-induced cocaine craving.

OBJECTIVE: Since signals for cocaine induce limbic brain activation in animals and cocaine craving in humans, the objective of this study was to test whether limbic activation occurs during cue-induced craving in humans. METHOD: Using positron emission tomography, the researchers measured relative regional cerebral blood flow (CBF) in limbic and comparison brain regions of 14 detoxified male cocaine users and six cocaine-naive comparison subjects during exposure to both non-drug-related and cocaine-related videos and during resting baseline conditions. RESULTS: During the cocaine video, the cocaine users experienced craving and showed a pattern of increases in limbic (amygdala and anterior cingulate) CBF and decreases in basal ganglia CBF relative to their responses to the non-drug video. This pattern did not occur in the cocaine-naive comparison subjects, and the two groups did not differ in their responses in the comparison regions (i.e., the dorsolateral prefrontal cortex, cerebellum, thalamus, and visual cortex). CONCLUSIONS: These findings indicate that limbic activation is one component of cue-induced cocaine craving. Limbic activation may be similarly involved in appetitive craving for other drugs and for natural rewards.

Striatal dopamine transporters and cognitive functioning in healthy men and women.

OBJECTIVE: There is growing interest in distinguishing the biological bases of sex differences in behavior from environmental influences. Sex hormone levels seem to be related to some cognitive abilities, particularly memory, and the dopaminergic system participates in the mediation of memory. The dopamine transporter is the primary indicator of dopaminergic tone. This study investigated the relationship between cognition and dopamine transporter availability in healthy men and women. METHOD: Dopamine transporter levels were measured with a technetium-99m radiolabeled analog of cocaine, TRODAT-1, in 66 healthy volunteers (30 men and 36 women). A neuropsychological battery designed to target functions associated with dopaminergic activity was administered during the uptake interval between the radiopharmaceutical injection and image acquisition. RESULTS: Women and younger participants had higher dopamine availability in the caudate nucleus, and these groups also performed better on verbal learning tasks. Furthermore, dopamine transporter availability was correlated with learning performance within groups. Relationships between dopamine availability in the caudate and putamen and executive and motor functioning were observed in women, but not in men. CONCLUSIONS: The results provide further evidence for age effects and sex differences in the neuromodulatory influences of dopamine on behavior in humans.

Clinical subtypes of schizophrenia: differences in brain and CSF volume.

OBJECTIVE: Investigations of the relation of clinical features of schizophrenia to neuroanatomic measures have produced inconclusive results. The purpose of this study was to examine measures of whole-brain volume in men and women and relate them to clinical subtypes of schizophrenia. METHOD: Magnetic resonance imaging measures of cranial, brain, and ventricular and sulcal CSF volume were examined in 81 patients with schizophrenia (50 men and 31 women), divided into subgroups based on their symptom profiles, and 81 demographically matched healthy comparison subjects. RESULTS: The men had higher cranial and brain volumes than the women. The patients had smaller cranial and brain volumes than the comparison subjects; they also had higher ventricular CSF volumes and thus higher ventricle-brain ratios (VBRs). Ratio elevations were larger for the female than for the male schizophrenic patients. The patients with predominantly negative symptoms of schizophrenia had higher VBRs and sulcal CSF-brains ratios than the comparison subjects, although the component volumes did not differ. The patients with predominantly Schneiderian symptoms had higher VBRs than the comparison subjects but showed reduced cranial and brain volumes. The paranoid patients had normal VBRs, reduced sulcal CSF-brain ratios, and lower cranial and sulcal CSF volumes. CONCLUSIONS: The results suggest two patterns of neuroanatomic whole-brain abnormalities that differ in severity according to the relative prominence of negative, Schneiderian, and paranoid symptoms. These patterns may reflect differential involvement of dysgenic and atrophic pathophysiological processes. Sex moderates abnormalities in the neuroanatomic features of schizophrenia.

Relations among clinical scales in schizophrenia.

OBJECTIVE: Clinical scales have become established as tools to quantify phenomenological features of schizophrenia. The goal of this study was to examine relations among the following: the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the deficit-nondeficit classification. METHOD: Forty-seven patients with schizophrenia were recruited according to specific inclusion and exclusion criteria. The standardized assessment procedures were administered by a trained psychiatric research team. RESULTS: Examination of the BPRS showed that the patients had highest scores on the thought disorder factor and the symptoms specific to schizophrenia. Classification of patients as having the positive, negative, or mixed type of schizophrenia resulted in a finding of seven with the positive, seven with the negative, and 33 with the mixed type. The division of patients into those with the deficit syndrome (N = 29) and those without (N = 18) was related to symptom specificity and to positive and negative symptoms. Deficit syndrome patients had more symptoms specific to schizophrenia, fewer nonspecific symptoms, and, as expected, greater severity of negative symptoms. Cluster analysis revealed three clusters of patients: those with low negative symptom scores and high scores on specific symptoms (the majority were without the deficit syndrome); those with high scores on negative, positive, and specific symptoms (the majority had the deficit syndrome); and those with lower scores on specific symptoms and high scores on negative and positive symptoms (the majority had the deficit syndrome). CONCLUSIONS: The scales showed some overlap but also seemed to measure complementary aspects of the phenomenology of schizophrenia. Subtypes of patients identified by the combined use of these scales may differ in underlying pathology.

Cerebral blood flow changes in limbic regions induced by unsolvable anagram tasks.

OBJECTIVE: The study addressed the question of whether unsolvable as opposed to solvable cognitive problems activate discrete neuronal systems in the human brain. METHOD: Twelve healthy humans tried to solve unsolvable anagrams. Solvable anagrams and a resting baseline after each anagram task served as control conditions in a within-subject design. Activation was measured with the equilibrium infusion method by using 15O-labeled water and positron emission tomography, with absolute quantitation of anatomically defined regional cerebral blood flow (CBF). RESULTS: Compared to rest, both anagram tasks increased activity in frontal and temporal regions. The soluble task condition increased hippocampal activation and decreased mammillary bodies activity, while unsolvable anagrams were associated with increased CBF to the mamillary bodies and amygdala and decreased hippocampal activity. CONCLUSIONS: A limbic network integrating negative emotion and cognition seems reflected in reciprocal diencephalic and limbic activation with solvable and unsolvable anagrams. Since unsolvable anagrams have been used to induce learned helplessness in humans, this finding may provide an initial step toward clarifying its neural substrate.

Striatal dopamine transporter binding assessed by [I-123]IPT and single photon emission computed tomography in patients with early Parkinson's disease: implications for a preclinical diagnosis.

BACKGROUND: Specific binding to dopamine transporters may serve as a tool to detect early loss of nigrostriatal dopaminergic neurons in patients with Parkinson's disease. OBJECTIVE: To determine striatal dopamine transporter binding using the cocaine analogue [I-123]N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chl orophenyl) tropane ([I-123]IPT) and single photon emission computed tomography. PATIENTS AND METHODS: We studied 9 control subjects (mean age, 58 years; range, 41-69 years) and 28 patients with early Parkinson's disease (Hoehn and Yahr stages I [n = 14] and II [n = 14] [symptom duration, <5 years]; mean age, 55.5 years; range, 36-71 years). Single photon emission computed tomography was performed 90 minutes after injection of 120 to 150 MBq of radioactive [I-123]IPT. RESULTS: Specific striatal [I-123] IPT binding (mean +/- SD) was significantly reduced in patients with early Parkinson's disease (ipsilateral striatum: 4.09+/-0.97; range, 2.46-6.40; contralateral striatum: 3.32+/-0.76; range, 1.80-5.13) compared with controls (left striatum: 7.28+/-0.94; range, 5.78-8.81; right striatum: 7.41+/-1.28; range, 5.58-9.44). IPT binding ratios (mean +/- SD) were significantly lower in patients with Hoehn and Yahr stage II (ipsilateral striatum: 3.47+/-0.75; contralateral striatum: 2.96+/-0.73) compared with those with Hoehn and Yahr stage I (ipsilateral striatum: 4.72+/-0.75; contralateral striatum: 3.69+/-0.61) (P<.001). The ipsilateral striatum of patients with Hoehn and Yahr stage I showed a significant mean+/-SD reduction of IPT binding (ipsilateral striatum: 4.72+/-0.75) compared with either right or left striatum of controls (P<.001). Only in 1 patient was IPT binding to the ipsilateral striatum (ratio, 6.40) higher than the lowest value observed in the striatum of a control subject (ratio, 5.58). CONCLUSIONS: Use of [I-123] IPT and single photon emission computed tomography demonstrates a reduction of dopamine transporter binding in patients with early Parkinson's disease. Significantly reduced IPT binding already observed in the ipsilateral striatum of patients with Hoehn and Yahr stage I demonstrates the potential of this method to detect preclinical disease.

Synthesis and characterization of technetium-99m-labeled tropanes as dopamine transporter-imaging agents.

In the development of novel Tc-99m-labeled tropane derivatives as dopamine transporter (reuptake site)-imaging agents, a series of neutral and lipophilic complexes containing bis-(aminoethanethiol) as a neutral complexing moiety for a [99mTc]TcO3+ center core was successfully prepared. Biological evaluation of the Tc-99m-labeled complexes 13-16 as central nervous system (CNS) dopamine transporter-imaging agents was reported. Synthesis of the tropane derivatives was achieved by stepwise reactions adding two aminoethanethiol units. The final free thiol ligands were obtained by deblocking the 4-methoxybenzyl protecting group with Hg(OAc)2 to obtain trifluoroacetate salts. All of the Tc-99m complexes, with the exception of 16, displayed good initial brain uptake and selective uptake in the striatal area, where dopamine transporters are concentrated. One of the compounds, [2-[[2-[[[3-(4-chlorophenyl)-8-methyl-8-azabicyclo [3.2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethy] amino]ethanethiolato-(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)]- [99mTc]technetium,[99mTc]TRODAT-1 (13), displayed the highest initial uptake in rat brain (0.4% at 2 min post iv injection); the striatal/cerebellar (ST/ CB) ratio reached 2.8 at 60 min after an iv injection. The specific uptake in rat brain can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; iv, 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal uptake was not affected by pretreating rats with a noncompeting ligand, haldol (iv, 1 mg/kg). After an iv injection of 9 mCi of [99mTc]TRODAT-1 (13), in vivo images of baboon brain using single-photon emission-computed tomography exhibited excellent localization in striatum (basal ganglia), where dopamine neurons are known to be concentrated. This series of compounds may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS diseases (i.e., Parkinson's disease) in which changes in the dopamine transporter concentration are implicated.

Ipsilateral and contralateral thalamic hypometabolism as a predictor of outcome after temporal lobectomy for seizures.

UNLABELLED: FDG PET is often used to help localize the seizure focus before surgery in patients with medically refractory temporal lobe epilepsy. However, the ability of certain patterns of metabolic landscape to predict postsurgical seizure outcome has not been well characterized. The purpose of this retrospective study was to determine whether FDG PET abnormalities elsewhere in the brain, in combination with those in the temporal lobes, can be used to predict seizure outcome after surgery. METHODS: Eighty patients with refractory temporal lobe seizures were imaged with PET after intravenous administration of 115 microCi/kg FDG. Images were interpreted without knowledge of clinical information by an experienced reviewer to determine seizure focus and regional metabolic changes in the brain. Metabolic activity scores were assigned for cortical and subcortical structures using the following criteria: 4 = normal activity, 3 = mildly decreased activity, 2 = moderately decreased activity, 1 = severely decreased activity, and 0 = no activity. A laterality index for each region was calculated using the equation 100 x [right - left]/[1/2 x (right + left)]. Seizure focus localization was based on the laterality of temporal lobe metabolic activity and was compared with that determined by scalp and depth electrodes and MRI results. Comparisons were made between asymmetries in metabolic activity in various brain structures and postoperative seizure frequency. Postoperative outcome was determined on the basis of cessation (complete disappearance of seizures) or continuation of seizure activity, regardless of frequency, compared with the preoperative state. RESULTS: All 64 patients who were free of seizures postoperatively had either no thalamic asymmetry or reduced metabolism on the side from which the temporal lobe was removed. In contrast, 5 of 16 patients (31%) with postoperative seizures of any frequency had hypometabolism in the thalamus contralateral to that of the removed temporal lobe. All 5 patients with reverse thalamic asymmetry had postoperative seizures. Patients with thalamic hypometabolism ipsilateral to the removed temporal lobe also had an increased risk of postoperative seizures, but this risk was not as high as in patients with the contralateral abnormality. In these patients, the temporal lobe (which appeared hypometabolic on PET) was determined to be the site of the seizure on the basis of information besides that provided by PET before surgery. CONCLUSION: This study indicated that, in patients with temporal lobe epilepsy, thalamic metabolic asymmetry, particularly in the reverse direction to that of the temporal lobe asymmetry, was associated with a poor postsurgical outcome compared with no or matched asymmetry. This determination may be important in evaluating patients for, and selecting optimal candidates for, surgical intervention.

The efficacy of iodine-123-MIBG as a screening test for pheochromocytoma.

UNLABELLED: The primary objective of this study was to characterize the effectiveness of 123I-metaiodobenzylguanidine (MIBG) as a screening test for pheochromocytoma in routine clinical practice. An attempt was made to determine why some tumors and some adrenal glands without pheochromocytoma minimally manifest increased uptake. METHODS: Planar images were obtained with a standardized protocol in a diverse group of patients. The intensity of uptake in each adrenal gland was graded on a 0-3-point scale by using the intensity of activity in the liver as a reference. Follow-up data were obtained from both the patients and the referring physicians. A final diagnosis was eventually established in 120 patients who had a total of 238 adrenal glands. RESULTS: There was an intramedullary pheochromocytoma in 24 of the 238 adrenal glands (10.1%). The uptake was very intense (Grade 3) in 21 of them (87.5%). The uptake was only mildly to moderately increased in the other three intra-adrenal tumors. There was no visible uptake in 148 of the 214 (69.2%) adrenals without a pheochromocytoma, but there was mildly to moderately increased activity in 66 (30.8%). There were no other features of the clinical data base which could differentiate between mildly increased uptake in a pheochromocytoma and mildly increased activity in a gland without a tumor, including the 24-hr urinary excretion of catecholamines. CONCLUSIONS: Since every intra- and extra-adrenal tumor was visualized, the findings suggest that 123I-MIBG may be the most sensitive screening test available for diagnosing pheochromocytoma. The test results should be definitive in most patients.

Cholescintigraphy in the diagnosis of acute cholecystitis: morphine augmentation is superior to delayed imaging.

Morphine-augmented radionuclide hepatobiliary imaging has been used as an alternative to delayed imaging for the diagnosis of acute cholecystitis. Previous studies have indicated that the morphine-augmentation is as useful as, or more useful than, delayed imaging. A careful comparison of the efficacy of the two techniques appears warranted because: (1) most early studies did not compare the efficacy of the two techniques in a single report using comparable patient populations; (2) the reported efficacy of morphine-augmentation is based primarily on study designs which excluded cases of early gallbladder visualization without morphine, while most delayed imaging protocols included these cases; and (3) there were concerns about the potential consequences of a false-negative morphine examination. This study compared the efficacy of morphine-augmentation with delayed imaging in those cases in which the gallbladder was not visualized during the first hour of study. Of 306 consecutive patients who were scanned to rule out acute cholecystitis, the gallbladder was visualized within 1 hr in 215 cases. In the remaining 91 cases, 46 patients had delayed imaging (17 true-positive, 10 true-negative, 19 false-positive and 0 false-negative), and 45 had morphine-augmentation (24 true-positive, 15 true-negative, 4 false-positive and 2 false-negative). The data indicate that delayed imaging has a significantly lower specificity and positive-predictive value for acute cholecystitis than morphine-augmentation and a slightly higher (statistically insignificant) sensitivity and negative-predictive value. These results appear to be supported by a reanalysis of the data that has already been reported in the literature.