Template images for nonhuman primate neuroimaging: 1. Baboon.

Coregistration of functional brain images across many subjects offers several experimental advantages and is widely used for studies in humans. Voxel-based coregistration methods require a high-quality 3-D template image, preferably one that corresponds to a published atlas. Template images are available for human, but we could not find an appropriate template for neuroimaging studies in baboon. Here we describe the formation of a T1-weighted structural MR template image and a PET blood flow template, derived from 9 and 7 baboons, respectively. Custom software aligns individual MR images to the MRI template; human supervision is needed only to initially estimate any gross rotational misalignment. In these aligned individual images, internal subcortical fiducial points correspond closely to a photomicrographic baboon atlas with an average error of 1.53 mm. Cortical test points showed a mean error of 1.99 mm compared to the mean location for each point. Alignment of individual PET blood flow images directly to the PET template was compared to a two-step alignment process via each subject's MR image. The two transformations were identical within 0.41 mm, 0.54 degrees, and 1.0% (translation, rotation, and linear stretch; mean). These quantities provide a check on the validity of the alignment software as well as of the template images. The baboon structural MR and blood flow PET templates are available on the Internet (purl.org/net/kbmd/b2k) and can be used as targets for any image registration software.

Evaluation of a reduced MR imaging sequencing protocol in adult patients with stroke.

PURPOSE: To compare a reduced (three-sequence) magnetic resonance (MR) imaging protocol with a full (eight- to 10-sequence) MR imaging protocol in adults suspected of having stroke. MATERIALS AND METHODS: Six neuroradiologists interpreted a consecutive sample of 265 MR images in patients suspected of having stroke. Each read reduced-protocol images in a discrete series of 40 patients (one read images in only 15) and corresponding full-protocol images 1 month later (reduced/full protocol). Five of the readers each read images in 10 additional cases, five each as full/full and reduced/reduced protocol controls. kappa values between full and reduced protocols, reader assessment of protocol adequacy, confidence level, and need for additional sequences or examinations were evaluated. RESULTS: In the reduced/full protocol, the kappa value for detecting ischemia was 0.797; and that for detecting any clinically important abnormality, 0.635. Statistically similar kappa values were found with the full/full control design (kappa = 0.802 and 0.715, respectively). The full protocol was judged more adequate than the reduced protocol (2.0 of 5.0 points vs 1.6, P <.001) and generated greater diagnostic confidence (8.6 of 10.0 points vs 8.9, P =.01), less need for additional sequences (2.7 of 6.0 points vs 1.5, P <.001), and more requests for additional examinations (28.4% vs 36.3%). CONCLUSION: Disagreement between interpretations of reduced- and full-protocol images might be attributable to baseline-level intraobserver inconsistency, as demonstrated in control designs. A greater number of sequences did not lead to greater consistency.

Dopamine D(1) agonist activates temporal lobe structures in primates.

Changes in the function of dopamine D(1)-influenced neuronal pathways may be important to the pathophysiology of several human diseases. We recently developed methods for averaging functional imaging data across nonhuman primate subjects; in this study, we apply this method for the first time to map brain responses to experimental dopamine agonists in vivo. Here we report the use of positron emission tomography (PET) in seven normal baboons to measure the regional cerebral blood flow (rCBF) responses produced by an acute dose of the dopamine D(1) full agonist SKF82958. The most significant rCBF increases were in bilateral temporal lobe, including amygdala and superior temporal sulcus (6-17%, P < 0.001). Blood flow decreased in thalamus, pallidum, and pons (4-7%, P = 0.001). Furthermore the rCBF responses were dose-dependent and had a half-life of approximately 30 min, similar to that reported for the drug's antiparkinsonian effects. Absolute whole-brain blood flow did not change, suggesting that these local changes in rCBF reflect neuronal rather than direct vascular effects of the agonist. The prominent temporal lobe response to a D(1) agonist supports and extends our recent observations that levodopa produces prominent amygdala activation both in humans and in other primates. We speculate that levodopa may exert its known effects on mood in humans through increased amygdala activity, mediated in part by D(1) receptors.

Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression.

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Amygdala core nuclei volumes are decreased in recurrent major depression.

The amygdala is a key structure in the brain's integration of emotional meaning with perception and experience. Patients with depression have impaired functioning in emotional tasks involving the amygdala, and have abnormal resting amygdala blood flow. To better understand the anatomical basis for these functional changes we measured the volumes of the total amygdala and of the core amygdala nuclei in 20 patients with a history of depression and 20 pair-wise matched controls. Depressed subjects had bilaterally reduced amygdala core nuclei volumes and no significant differences in total amygdala volumes or in whole brain volumes. Since patients with a depression history have bilateral hippocampal volume reduction the volume loss in this closely related structure suggests a shared effect on both structures, potentially glucocorticoid-induced neurotoxicity mediated by the extensive reciprocal glutamatergic connections.

Baboon basal ganglia stereotaxy using internal MRI landmarks: validation and application to PET imaging.

PURPOSE: We report the residual anatomic error after a nine parameter visually guided registration of MR images with a baboon brain atlas to validate a stereotactic method for use in PET studies. METHOD: MPRAGE images of brain in six baboons and one nemestrina monkey were placed in atlas space using internal landmarks and proportional measurements. An expert noted the location of 23 subcortical test points in the transformed images and in the atlas. RESULTS: The average absolute error at the test points was 1.62 mm. At the extremes of the brain surface, there was more variability. PET images could be combined across animals in a common atlas space. CONCLUSION: There is minimal subcortical error attributable to anatomic variability after this method of transforming MR images of baboon to stereotactic space. This method provides a useful tool for intrasubject PET baboon studies as well as "bootstrapping" for more refined methods.

PET measurement of dopamine D2 receptor-mediated changes in striatopallidal function.

This study was designed to validate an in vivo measurement of the functional sensitivity of basal ganglia neuronal circuits containing dopamine D2 receptors. We hypothesized that a D2 agonist would decrease striatopallidal neuronal activity, and hence regional cerebral blood flow (rCBF) over the axon terminals in the globus pallidus. Quantitative pallidal blood flow was measured using positron emission tomography (PET) with bolus injections of H215O and arterial sampling in six baboons before and after intravenous administration of the selective D2 agonist U91356a. We also tested whether the response to U91356a was modified by previous acute administration of various antagonists. Another baboon had serial measurements of blood flow under identical conditions, but received no dopaminergic drugs. In all animals that received U91356a, pallidal flow decreased in a dose-related manner. Global CBF had a similar response, but the decline in pallidal flow was greater in magnitude and remained significant after accounting for the global effect. A D2 antagonist, but not antagonists of D1, serotonin-2, or peripheral D2 receptors, prevented this decrease. This work demonstrates and validates an in vivo measure of the sensitivity of D2-mediated basal ganglia pathways. It also supports the hypothesis that activation of the indirect striatopallidal pathway, previously demonstrated using nonselective D2-like agonists, can be mediated specifically by D2 receptors. We speculate that the U91356a-PET technique may prove useful in detecting functional abnormalities of D2-mediated dopaminergic function in diseases such as parkinsonism, dystonia, Tourette syndrome, or schizophrenia.

Stereological MRI volumetry of the frontal lobe.

Stereology was used to measure frontal lobe volume on magnetic resonance imaging (MRI) scans in a multi-observer repeated-measures trial in 17 adults. Prior to measurement, MR image volumes were reoriented into coronal sections perpendicular to the bicommissural plane. Three observers blinded to subject identify repeatedly used fixed grid stereology to estimate frontal lobe volumes, defined as all sections of the frontal lobe anterior to the anterior commissure. The lateral ventricles were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was 0.03. The inter-rater correlation coefficient = 0.95 for three raters; intra-rater correlation coefficients = 0.95-0.98. A comparison was made between stereological and traditional edge tracing measurement of the frontal lobe volumes. The overall correlation between the two methods was 0.95. The use of internal landmarks to define orientation and 3-D orthogonal views to define frontal lobe boundaries on 3-D images was critical to obtaining repeatable measurements. Frontal lobe volumetry by brain MR used to estimate small differences postulated to occur in certain psychiatric and neurologic disorders requires high precision and repeatability. Stereology, a semi-automated method, can reliably estimate frontal lobe volumes. This method may distinguish small frontal lobe volume differences within individuals and between groups.

Comparison of clinical evaluation and computed tomographic diagnostic accuracy for tumors of the larynx and hypopharynx.

Ninety-five patients with laryngeal and hypopharyngeal cancer were examined and staged preoperatively by clinical evaluation (CE) and computed tomography (CT). The CE and CT staging were compared to each other and to the pathologic (PT) staging of the tumors. The CT staging showed high accuracy in staging transglottic (88%), supraglottic (68%), and oropharyngeal tumors invading the larynx (68%) when compared to the PT findings. The CT staging was less effective in evaluating glottic tumors (46%), both overstaging (12%) and understaging (20%) cases. Combined CE-CT evaluation showed higher accuracy in staging all tumors (84%) compared to CE alone (52%) or CT alone (68%). The findings suggest that combined CE-CT should be used to evaluate laryngeal and hypopharyngeal tumors.

Hippocampal atrophy in recurrent major depression.

Hippocampal volumes of subjects with a history of major depressive episodes but currently in remission and with no known medical comorbidity were compared to matched normal controls by using volumetric magnetic resonance images. Subjects with a history of major depression had significantly smaller left and right hippocampal volumes with no differences in total cerebral volumes. The degree of hippocampal volume reduction correlated with total duration of major depression. In addition, large (diameter > or = 4.5 mm)-hippocampal low signal foci (LSF) were found within the hippocampus, and their number also correlated with the total number of days depressed. These results suggest that depression is associated with hippocampal atrophy, perhaps due to a progressive process mediated by glucocorticoid neurotoxicity.

Craniosynostosis: diagnostic imaging with three-dimensional CT presentation.

PURPOSE: To measure diagnostic performance and preference of two three-dimensional CT reconstruction modalities (voxel-gradient and surface-projection) displayed two ways (conventional and unwrapped) in craniosynostosis confirmed by surgical inspection and histologic analysis of resected sutures. METHODS: High-resolution 2-mm contiguous CT sections were obtained and three-dimensional reconstruction images generated for 25 infants and children with skull deformities before surgical treatment of craniosynostosis. Two pediatric radiologists and two neuroradiologists first ranked images by their own preferences for diagnostic use. Then they diagnosed craniosynostosis from images presented in random order and blinded. The standard of reference was inspection during surgery and histologic evaluation of excised sutures. Finally, reviewers repeated their subjective preference tests. RESULTS: The least experienced radiologist had 100% sensitivity for all imaging modalities and specificities ranging from 43% to 83%. The two most experienced radiologists performed nearly identically, with sensitivities of 96% and specificities of 100%. After performing diagnostic tasks using all image types, all radiologists preferred conventional surface projections. CONCLUSION: Experienced readers can achieve nearly perfect diagnostic performance using the latest three-dimensional CT reconstruction images, making it a contribution to the diagnostic process. Although performance is nearly identical for all modalities, readers strongly prefer conventionally presented surface-projection images.

Binary nature and radiographic identifiability of craniosynostosis.

RATIONALE AND OBJECTIVES: Two independent gold standards and diagnoses from three-dimensional computed tomography (CT) images were used to examine the possibility that craniosynostosis is a binary abnormality that potentially may be diagnosed without error. METHODS: Surgical reports, histology of excised sutures, and three-dimensional CT images were compared for 25 children undergoing surgical management of craniosynostosis. Surgical reports identified sutures as normal or abnormal. Histology reported suture closure on a 5-point scale. Four radiologists used three-dimensional CT images to diagnose sutures on a 6-point rated response scale. RESULTS: Sutures with histology 0, 1, or 2 were normal on surgical reports, and those with histology 3 or 4 were abnormal. Most readers achieved nearly perfect sensitivity and specificity. Reader confidence was unrelated to degree of pathology. CONCLUSION: Craniosynostosis appears to be binary in our sample. Surgical reports, pathology results, and three-dimensional CT images read by experienced viewers achieved nearly perfect agreement.

Tracer-kinetic analysis for measuring regional cerebral blood flow by dynamic nuclear magnetic resonance imaging.

Measurement of regional cerebral blood flow in vivo has proved useful in the study of normal and diseased states in the brain. This circumstance has led to a variety of techniques for its quantitative determination and has continued to motivate the search for ever safer and more accurate methods of measurement. Recently, the use of nuclear magnetic resonance (NMR) in medical imaging has stimulated efforts to make it the basis for a non-invasive method of measuring flow in the brain. New advances in fast NMR imaging (MRI) provide data potentially amenable to analysis by tracer-kinetic methods. Such an analysis has not previously been available. In this paper we present theoretical results that may permit measurement of brain blood flow by NMR. The data interpreted by our model are those generated by a novel MRI protocol developed by Perman et al. (1992, Magn. Reson. Med. 28, 74-83; Radiology 185(P), Abstr. 154, 127) that is entirely compatible with existing routine MRI procedures. These data are fast dynamic NMR signals that reflect passage of an intravenously administered paramagnetic contrast agent serving as a plasma tracer. Our equations show how to use such data sequences to determine plasma mean transit time, plasma volume, and plasma and whole-blood flow in arbitrarily selected regions of interest in the brain. The theory accounts rigorously for recirculation of tracer to the imaged regions. Our analysis provides an explanation for the linear relationship observed experimentally by others between regional vascular volumes and time integrals of vascular-tracer residue curves, and shows that this relationship remains valid in the presence of tracer recirculation.

Infected epidermoid cyst of the sphenoid bone.

An infected epidermoid cyst presented on CT as a primarily dense, sclerotic expansile lesion in the greater wing of the sphenoid bone. Presumably, infection was responsible for the atypical appearance.

A half-Fourier gradient echo technique for dynamic MR imaging.

Recently we developed the simultaneous dual FLASH (SDFLASH) pulse sequence that simultaneously obtains sequential images from the brain and the internal-carotid arteries in the neck with 1-sec temporal resolution using a standard MR scanner. The high temporal resolution (1 sec) of the SDFLASH technique was achieved partly by using a low number of phase-encoding views which thereby limited our in-plane spatial resolution to 6.25 x 3.12 mm pixels. To overcome this limitation we have developed a calibration technique which corrects distortions in signal intensity and object shape when using gradient echo half-Fourier spin warp imaging. Using this calibration technique, the operator can use the 41% decrease in scan time to either double the spatial or temporal resolution. We have successfully used this technique to acquire SDFLASH images of the head and neck with 1.0 sec temporal resolution and 3.12 x 1.6 mm spatial resolution.

Simultaneous MR acquisition of arterial and brain signal-time curves.

Regional cerebral blood flow (rCBF) provides important information about local neuronal functional and cerebrovascular status. Determination of rCBF requires sequential measurements of tracer concentration in arterial blood and brain tissue unless the tracer is trapped in the brain in proportion to rCBF. Since gadopentate dimeglumine is not trapped within brain tissue, we have developed the simultaneous dual FLASH pulse sequence (SDFLASH) which sequentially measures the MR signal change in both the internal carotid artery and brain parenchyma simultaneously during the passage of a bolus of paramagnetic contrast material.

Senile dementia and healthy aging: a longitudinal CT study.

Volumetric indexes of cerebral atrophy obtained by using computed tomography (CT) were measured longitudinally in patients with senile dementia of the Alzheimer type (SDAT) and in healthy elderly control subjects. Measurements were made three times over a 51-month period. Of the original 44 patients with SDAT, five were available for CT examination at the last time of assessment (51 months); in contrast, 41 of the original 58 control subjects were still available for study at 51 months. As a group, scans of SDAT subjects showed greater atrophy than those of control subjects in all volumetric indexes at each time of testing and demonstrated greater progression of atrophy during the study period. However, the overlap of indexes between the patients with SDAT and the control subjects indicates that CT data cannot be used alone to predict the presence or progression of dementia in individual cases.

Clinical experience with ioversol 320 in cranial computed tomographic scanning.

Sixty patients referred to the Mallinckrodt Institute of Radiology at Washington University School of Medicine, St. Louis, participated in an open-label, noncomparative study of the safety, tolerance, and efficacy of the contrast agent ioversol 320 in cerebral computed tomographic (CCT) scanning. None of the patients experienced any drug-related, clinically significant changes in vital signs or any serious adverse reactions; nor did they report experiencing pain when the agent was injected intravenously. In addition, the radiographic quality of the scans was rated as excellent or good for patients who had enhanceable brain lesions. All CCT scans were considered diagnostic. In this series, ioversol 320 proved to be safe, well tolerated, and effective for use in CCT scanning.

Preoperative assessment of parotid masses: a comparative evaluation of radiologic techniques to histopathologic diagnosis.

A double-blind, retrospective analysis of 110 sequentially operated parotid masses compared the usefulness of preoperative radiologic evaluation to histopathologic diagnosis. The radiologic assessment included 25 sialograms, 162 computed tomography scans, and 10 nuclear magnetic resonance images. The diagnosis is influenced by the following four parameters of computed tomography: tumor borders, density, homogeneity, and enhancement. Well-defined borders, a homogeneous appearance, and high density strongly favor the diagnosis of a benign tumor or a low-grade malignancy (96.7%). Ill-defined tumor borders, heterogeneity, and high density indicate mainly a high-grade or recurrent malignancy (68.8%). Ill-defined borders, a heterogeneous appearance, and mixed density identify a lymphoepithelial lesion, lymphangioma, or sialoadenitis (100%). Sialography is cost effective in the evaluation of lymphoepithelial lesions. Computed tomography sialography offers no advantages over computed tomography with intravenous contrast. High-resolution computed tomography with intravenous contrast is highly sensitive for tumor detection (97%). Magnetic resonance imaging is complementary or superior to computed tomography (100%).

Osmotic demyelination syndrome. Lack of pathologic and radiologic imaging correlation.

An otherwise healthy diabetic woman developed severe hyponatremia, her serum sodium ion levels were rapidly corrected to normal, and she had a course of improvement then neurologic deterioration, with seizures and coma developing in the subsequent two days. Imaging studies, including computed tomography and magnetic resonance images of the brain as late as 19 days after the osmotic insult, failed to show pathologically demonstrated demyelinating lesions. Osmotic brain injury induces demyelination in areas of gray-white apposition and, clinically, results in a delayed neurologic deterioration one to three days following the osmotic challenge. Even with magnetic resonance imaging, review of the literature and this experience suggest that osmotic demyelination cannot reliably be imaged during the first month after the insult.