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The introduction of mild cognitive impairment (MCI) as a diagnostic category adds to the challenges of diagnosing Alzheimer’s Disease (AD). No single marker has been proven to accurately categorize patients into their respective diagnostic groups. Thus, previous studies have attempted to develop fused predictors of AD and MCI. These studies have two main limitations. Most do not simultaneously consider all diagnostic categories and provide suboptimal fused representations using the same set of modalities for prediction of all classes. In this work, we present a combined framework, cascaded multiview canonical correlation (CaMCCo), for fusion and cascaded classification that incorporates all diagnostic categories and optimizes classification by selectively combining a subset of modalities at each level of the cascade. CaMCCo is evaluated on a data cohort comprising 149 patients for whom neurophysiological, neuroimaging, proteomic and genomic data were available. Results suggest that fusion of select modalities for each classification task outperforms (mean AUC = 0.92) fusion of all modalities (mean AUC = 0.54) and individual modalities (mean AUC = 0.90, 0.53, 0.71, 0.73, 0.62, 0.68). In addition, CaMCCo outperforms all other multi-class classification methods for MCI prediction (PPV: 0.80 vs. 0.67, 0.63).

ObjectiveTo study longitudinal relationships between type 2 diabetes mellitus (T2DM), cortical thickness, and cognitive function in older people with normal cognition, mild cognitive impairment, and Alzheimer disease (AD).MethodsThe sample was derived from the Alzheimer's Disease Neuroimaging Initiative cohort who underwent brain MRI and cognitive tests annually for 5 years. Presence of T2DM was based on fasting blood glucose ≥7.0mml/L or the use of glucose-lowering agents. We used latent growth curve modeling to explore longitudinal relationships between T2DM, cortical thickness, and cognitive function, adjusting for relevant covariates and testing for interactions.ResultsThere were 124 people with T2DM (mean age 75.5 years, SD 6.2) and 693 without T2DM (mean age 75.1 years, SD 6.9) with at least 1 MRI available. AD and lower cortical thickness at study entry was associated with a lower chance of having a MRI available at each follow-up phase (all p < 0.001). T2DM was associated with lower baseline cortical thickness (p = 0.01). We found no direct effect of T2DM on decline in cortical thickness or cognitive function, but there was an indirect pathway linking T2DM and cognitive decline via baseline cortical thickness (β = −0.17, p = 0.022). There was an interaction between T2DM and education whereby the negative effect of T2DM on baseline cortical thickness was reduced in those with greater education (β = 0.34, p = 0.037). These associations changed minimally when adjusted for baseline cognitive diagnosis.ConclusionsIn an older cohort with low cerebrovascular disease burden, T2DM contributes to cognitive decline via neurodegeneration. Prior brain and cognitive reserve may protect against this effect.

Accurate diagnosis of mild cognitive impairment (MCI) before conversion to Alzheimer’s disease (AD) is invaluable for patient treatment. Many works showed that MCI and AD affect functional and structural connections between brain regions as well as the shape of cortical regions. However, ‘shape connections’ between brain regions are rarely investigated -e.g., how morphological attributes such as cortical thickness and sulcal depth of a specific brain region change in relation to morphological attributes in other regions. To fill this gap, we unprecedentedly design morphological brain multiplexes for late MCI/AD classification. Specifically, we use structural T1-w MRI to define morphological brain networks, each quantifying similarity in morphology between different cortical regions for a specific cortical attribute. Then, we define a brain multiplex where each intra-layer represents the morphological connectivity network of a specific cortical attribute, and each inter-layer encodes the similarity between two consecutive intra-layers. A significant performance gain is achieved when using the multiplex architecture in comparison to other conventional network analysis architectures. We also leverage this architecture to discover morphological connectional biomarkers fingerprinting the difference between late MCI and AD stages, which included the right entorhinal cortex and right caudal middle frontal gyrus.

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the $${\ell }_{{\bf{1}}}$$ ℓ 1 -norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce the estimation bias in regression tasks. But using them in SCCA remains largely unexplored. In this paper, we design a unified non-convex SCCA model, based on seven non-convex functions, for unbiased estimation and stable feature selection simultaneously. We also propose an efficient optimization algorithm. The proposed method obtains both higher correlation coefficients and better canonical loading patterns. Specifically, these SCCA methods with non-convex penalties discover a strong association between the APOE e4 rs429358 SNP and the hippocampus region of the brain. They both are Alzheimer’s disease related biomarkers, indicating the potential and power of the non-convex methods in brain imaging genetics.

Accurate prediction of Alzheimer’s disease (AD) is important for the early diagnosis and treatment of this condition. Mild cognitive impairment (MCI) is an early stage of AD. Therefore, patients with MCI who are at high risk of fully developing AD should be identified to accurately predict AD. However, the relationship between brain images and AD is difficult to construct because of the complex characteristics of neuroimaging data. To address this problem, we present a longitudinal measurement of MCI brain images and a hierarchical classification method for AD prediction. Longitudinal images obtained from individuals with MCI were investigated to acquire important information on the longitudinal changes, which can be used to classify MCI subjects as either MCI conversion (MCIc) or MCI non-conversion (MCInc) individuals. Moreover, a hierarchical framework was introduced to the classifier to manage high feature dimensionality issues and incorporate spatial information for improving the prediction accuracy. The proposed method was evaluated using 131 patients with MCI (70 MCIc and 61 MCInc) based on MRI scans taken at different time points. Results showed that the proposed method achieved 79.4% accuracy for the classification of MCIc versus MCInc, thereby demonstrating very promising performance for AD prediction.

There is considerable debate whether Alzheimer's disease (AD) originates in basal forebrain or entorhinal cortex. Here we examined whether longitudinal decreases in basal forebrain and entorhinal cortex grey matter volume were interdependent and sequential. In a large cohort of age-matched older adults ranging from cognitively normal to AD, we demonstrate that basal forebrain volume predicts longitudinal entorhinal degeneration. Models of parallel degeneration or entorhinal origin received negligible support. We then integrated volumetric measures with an amyloid biomarker sensitive to pre-symptomatic AD pathology. Comparison between cognitively matched normal adult subgroups, delineated according to the amyloid biomarker, revealed abnormal degeneration in basal forebrain, but not entorhinal cortex. Abnormal degeneration in both basal forebrain and entorhinal cortex was only observed among prodromal (mildly amnestic) individuals. We provide evidence that basal forebrain pathology precedes and predicts both entorhinal pathology and memory impairment, challenging the widely held belief that AD has a cortical origin., Whether Alzheimer's disease originates in basal forebrain or entorhinal cortex remains highly debated. Here the authors use structural magnetic resonance data from a longitudinal sample of participants stratified by cerebrospinal biomarker and clinical diagnosis to show that tissue volume changes appear earlier in the basal forebrain than in the entorhinal cortex.

Background/aims: Increasing signal-to-noise ratio for skin spectroscopy means increasing area, but increased area usually means resorting to Fourier window techniques to prevent overwhelming muscle contamination. The aim of this work was to develop a simple coil that would allow large areas of skin to be sampled while limiting muscle contamination simply by the coil's geometry. Methods: The coil design was arrived at by using simulations that were calibrated by phantom tests with prototype units. It was then fabricated by using an etched circuitboard technique and tested on three volunteers for comparison with predicted performance. Results: The new coil acquires magnetic resonance signals from a 140 cm2 contoured layer of surface tissue with sufficient selectivity that 81% of the signal comes from tissue less than 1.9 mm deep. For skin and fat thicknesses of 1.1 and 3.1 mm, respectively, tending toward a worst case in-vivo situation, muscle contamination is only 3.3%. With the new coil, in 1 h, it was possible to directly acquire 31P skin spectra comparable to those formerly obtained in 4 h in two separate acquistions that then had to be subtracted to obtain the desired skin spectra. Conclusion: Increasing the area of skin sampled while maintaining selectivity to limit muscle contamination, relying simply on coil geometry, is practical using a parallel configuration of long narrow strip coils.

Background/aims: Characterization of skin phosphometabol-ism in vivo by non-invasive magnetic resonance spectroscopy (MRS) might allow assessment of ischemic or irradiative damage. Methods: Based on a study of 17 healthy volunteers, we present statistical analyses for intra- and inter-tissue metabolite concentration ratios, as well as for pH and [Mg2+]. Results: Results contrasted steady-state energy metabolism in skin and muscle, showing lower phosphocreatine/ATP, higher percentage of inorganic phosphate, phosphodiesters and phos-phomonoesters, and higher pH and [Mg2+] in skin than in muscle. Conclusion: Results were consistent with known skin physiology and structure and suggested an inverse relationship between skin phosphodiester levels and melanin.

While decreased ATP production and redox imbalance are central to mitochondrial disease pathogenesis, efforts to develop effective treatments have been hampered by the lack of imaging markers of oxidative stress. In this study we wished to determine if Tc99m-HMPAO, a SPECT imaging marker of cerebral blood flow and glutathione/protein thiol content, could be used to monitor the effect(s) of EPI-743, an oral redox modulating, para-benzoquinone based therapeutic for mitochondrial disease. We hypothesized that treatment changes in HMPAO uptake would be inversely proportional to changes in oxidative stress within the brain and directly correlate to clinical response to EPI-743 therapy. Twenty-two patients with mitochondrial disease were treated with EPI-743. Each underwent baseline and 3-month Tc99m-HMPAO SPECT scanning along with clinical/neurologic evaluations. Diseases treated were: Leigh syndrome (n=7), polymerase γ deficiency (n=5), MELAS (n=5), Friedreich ataxia (n=2), Kearns-Sayre syndrome, Pearson syndrome, and mtDNA depletion syndrome. Neuro-anatomic uptake analyses of HMPAO were performed with NeuroGam™ (Segami Corp.) statistical software and clinical response was assessed by the Newcastle Paediatric Mitochondrial Disease Scale or Newcastle Mitochondrial Disease Adult Scale depending on patient age. For all 22 patients there was a significant linear correlation between the change in cerebellar uptake of HMPAO and the improvement in Newcastle score (r=0.623, **p=0.00161). The MELAS subgroup showed a significant relationship of whole brain uptake (n=5, r=0.917, *p=0.028) to improvement in Newcastle score. We conclude that Tc99m-HMPAO SPECT scanning has promise as a general marker of the oxidative state of the brain and its response to redox modulating therapies. Further studies will be needed to confirm these findings in a more homogenous study population.

Introduction Use of electroconvulsive therapy (ECT) is limited by cognitive disturbance. Focal electrically-administered seizure therapy (FEAST) is designed to initiate focal seizures in the prefrontal cortex. To date, no studies have documented the effects of FEAST on regional cerebral blood flow (rCBF). Methods A 72 year old depressed man underwent three single photon emission computed tomography (SPECT) scans to capture the onset and resolution of seizures triggered with right unilateral FEAST. We used Bioimage Suite for within-subject statistical analyses of perfusion differences ictally and post-ictally compared with the baseline scan. Results Early ictal increases in regional cerebral blood flow (rCBF) were limited to the right prefrontal cortex. Post-ictally, perfusion was reduced in bilateral frontal and occipital cortices and increased in left motor and precuneus cortex. Conclusion FEAST appears to triggers focal onsets of seizure activity in the right prefrontal cortex with subsequent generalization. Future studies are needed on a larger sample.

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions., Late-onset Alzheimer's disease (LOAD) is a complex multi-factorial disorder. Here, the authors perform a data-driven analysis of LOAD progression, including multimodal brain imaging, plasma and CSF biomarkers, and find vascular dysfunction is among the earliest and strongest altered events.

Background: Patients with cirrhosis of the liver frequently present with many gastrointestinal complaints that are most likely due to abnormal gastrointestinal motility. The cause of these motility disorders in cirrhotics is unknown, however, underlying autonomic dysfunction may play a role. Objective: To determine the association between autonomic dysfunction and delayed gastric emptying in cirrhotic patients. Methods: We prospectively studied 20 patients with cirrhosis ofthe liver and postprandial abdominal pain, nausea, and vomiting and 10 asymptomatic patients with Hepatitis C (HCV) and no evidence of cirrhosis. All patients underwent 5 standardized cardiovascular tests to assess autonomic function. Each test was scored on a continuum from 0 (normal) to 5 (severe disease), thus producing a composite score of 0 to 5 for each subject. A composite score of greater than 1.5 was considered abnormal, with 5 representing severe autonomic involvement. A solid phase gastric emptying study was performed in each patient and a gastric retention ofgreater than 50% at 100 minutes was considered abnormal. Results: The mean percent retention at 100 minutes was 70.7% in the cirrhotic group vs. 26.1% (P < 0.001) in the patients with HCV and no evidence of cirrhosis (controls). The composite autonomic score for the cirrhotic group was 3.4 vs. 1.2 (P

Background: Functional neuroimaging studies after alcohol cessation have demonstrated that chronic alcohol use globally reduces neuronal activity for several weeks. Less is known about the effects of previous alcohol use patterns on regional brain activity. Multiple previous alcohol detoxifications are associated with a worse clinical course and increased risk of seizures, perhaps due to sensitization of key brain structures. We performed the following imaging study in alcoholics in the postwithdrawal period to determine if blood flow in medial temporal structures would differ as a function of previous alcohol use (i.e., whether regions were kindled or sensitized due to multiple detoxifications). Method: Fourteen adults meeting DSM-IV criteria for alcohol dependence (mean age 35, 8 SD; 10 men) and participating in a double-blind detoxification medication study underwent a brain perfusion Tc99 m-ECD (Neurolite) single photon emission computed tomography scan on days 7 through 9 (mean 7.6, .5 SD) after their last drink and 2 to 3 days since their last detoxification medication. Seven nonpsychiatrically ill, nonalcohol-dependent healthy adults were scanned as control subjects. Result: Alcoholics compared with controls had widely reduced relative activity in cortical secondary association areas and relatively increased activity in the medial temporal lobes (p < 0.01). Five alcoholic patients with ≥2 previous detoxifications were compared with five patients in their first detoxification (age and detoxification medication matched). Multiple detoxification patients had significantly lower relative activity in bilateral anterior temporal poles and medial temporal lobes and in visual cortex (p < 0.01) compared with first episode patients. Conclusions: These studies are consistent with other studies comparing alcoholics and controls. They also suggest that on day 7 of detoxification, alcoholic subjects with multiple previous detoxifications have decreased visual cortex, medial temporal lobes, and anterior paralimbic blood flow, compared with those in their first detoxification. Further studies seem warranted to confirm these initial exploratory results.

Although transcranial magnetic stimulation has been used as a stand-alone brain mapping tool, relatively few studies have attempted to couple TMS with functional brain imaging to understand the neurobiological effects of TMS. Technical problems of placing a TMS coil in a PET or MRI scanner have hampered previous efforts at imaging the immediate effects of TMS. Perfusion SPECT offers the advantage of tracer injection away from the camera, with later image development. We wondered if perfusion SPECT could be used to visualize brain changes during rTMS over the left prefrontal cortex—a region where rTMS has been shown to cause changes in mood or working memory. Eight healthy adult subjects were scanned with brain SPECT scintigraphy using 30 mCi (1110 MBq) Neurolite® (DuPont Pharma) on a triple-headed Picker camera. Each subject had three scans: (1) baseline, (2) bolus tracer injection during seconds 10–20 of a train of 2 min of left prefrontal rTMS (10 Hz; 60% motor threshold (MT); 10 s on/off, 600 stimuli) (2MIN), and (3) exactly as in the 2MIN, but immediately after subjects had received 18 min of high frequency stimulation (20 Hz; 80% MT; 2 s on/28 s off, 1440+600=2040 total stimuli) (20MIN). Scans were linearly transformed into Talairach space using SPM96b and compared across conditions (p R) and hypothalamus at 20 min and at 2 min, with thalamic increases occurring at the 20 min scan compared to baseline. There was an apparent TMS dose effect with twice as many decreases at 20 min than 2 min. Directly comparing the 20 min to the 2 min scans demonstrated opposite hemisphere decreases and relative increases in the ipsilateral (left) hemisphere as a function of more TMS stimuli. Full interpretation of these results is hampered by incomplete knowledge of the effect of the relative amount of stimulation to rest during tracer uptake, pharmacokinetics of tracer uptake, and depth and intensity of the magnetic field. Nevertheless, coupling rTMS with split-dose perfusion SPECT appears to be a promising method for understanding the brain changes associated with rTMS, and for directly visualizing neural circuits. We have demonstrated that prefrontal rTMS at high frequencies has both local and remote effects. These imaging results may help explain the cognitive and behavioural effects demonstrated in other prefrontal rTMS studies involving mood and working memory. Copyright © 1999 John Wiley & Sons, Ltd.

Background/aims: In recent decades, interest has increased in the chronological and environmental factors governing the aging of skin. Various methods have been used for determining water and lipid content of human skin as a function of subject age. Magnetic resonance chemical shift imaging (CSI) offers a noninvasive technique for observing detailed distributions of water, lipids and other chemicals in the skin, and thus may be useful in dermatogerontology. Methods: Human skin was examined in vivo on nine healthy volunteers, both male and female. Localized 1H spectra of the skin were obtained from voxels 78 μm thick and parallel to the skin surface. Unique water and lipid profiles were observed for different individuals, showing the composition and microstructure of epidermis, dermis and hypodermis in each subject. These allowed the quantification of skin thickness in vivo by the first appearance of triacylglyceride olefinic protons at the dermal-hy-podermal junction, or alternatively by the degree of lipid infiltration into dermis. Results: The relative concentration of free water in the skin, normalized to skin thickness, was observed to be slightly greater in older subjects and also in tanned subjects. More significantly, a microstructural feature common to every subject, i.e., the position of a possible capillary plexus in the dermis, showed migration toward the skin surface with advancing age. Conclusions: Such observations are consistent with previous studies of skin aging by other techniques and show promise for CSI in dermatogerontology as a non-invasive means for determination of skin water in vivo.

Purpose: In the effort to reduce radiation exposure to patients undergoing myocardial perfusion imaging (MPI) with SPECT/CT, we evaluate the feasibility of a single CT for attenuation correction (AC) of single-day rest (R)/stress (S) perfusion. Methods: Processing of 20 single isotope and 20 dual isotope MPI with perfusion defects were retrospectively repeated in three steps: (1) the standard method using a concurrent R-CT for AC of R-SPECT and S-CT for S-SPECT; (2) the standard method repeated; and (3) with the R-CT used for AC of S-SPECT, and the S-CT used for AC of R-SPECT. Intra-Class Correlation Coefficients (ICC) and Choen’s kappa were used to measure intra-operator variability in sum scoring. Results: The highest level of intra-operator reliability was seen with the reproduction of the sum rest score (SRS) and sum stress score (SSS) (ICC > 95%). ICCs were > 85% for SRS and SSS when alternate CTs were used for AC, but when sum difference scores were calculated, ICC values were much lower (~22% to 27%), which may imply that neither CT substitution resulted in a reproducible difference score. Similar results were seen when evaluating dichotomous outcomes (sum scores difference of ≥ 4) when comparing different processing techniques (kappas ~0.32 to 0.43). Conclusions: When a single CT is used for AC of both rest and stress SPECT, there is disproportionately high variability in sum scoring that is independent of user error. This information can be used to direct further investigation in radiation reduction for common imaging exams in nuclear medicine.

Atypical cortical degenerative syndromes of the non-Alzheimer's disease type are becoming increasingly recognized in the literature. Three cases consisting of primary progressive aphasia, posterior cortical atrophy, and frontal lobe dementia of the non-Alzheimer's type are presented to replicate and extend emerging literature. Detailed clinical description and neuropsychological data, coupled with confirmatory neurofunctional imaging, are presented to provide empirical support that specific inclusion and exclusion criteria can be applied to clinically diagnosis atypical degenerative cortical dementias.

Skin 31 P MRS measurements might detect metabolic damage from irradiation, chemotherapy, or ischemia. Although rat and cadaver data have demonstrated this potential (C. D. Cuono, et al., Plast. Reconstr. Surg. 81, 1-11 (1988), H. W. Klein, et al., Ann. Plast. Surg. 20, 547-551 (1988)), few studies of in vivo phosphorus human skin spectra have been published (A. Zemtsov, et al., J. Dermatol. Surg. Oncol. 15, 1207-1211 (1989), A Zemtsov, et al., J. Am. Acad. Dermatol. 30, 959-965 (1994)), and those likely reflect underlying muscle as much as skin. To separate 31 P skin and muscle spectra, we have developed a unique two-layer flotation phantom for mapping coil sensitivity and an associated semiempirical two-power RF depth-resolved technique. Phantom and method have been applied in a study of 17 normal volunteers to obtain human in vivo 31 P skin spectra uncompromised by muscle contamination and to quantitate ratios of major phosphometabolites. Skin results consistently showed low ratios of phosphocreatine (PCr) to adenosine triphosphate (ATP), high levels of phosphomonoester (PME), P i , and phosphodiester (PDE) relative to PCr, and demonstrated a shift in pH toward greater alkalinity, compared to that with simultaneous muscle results.

Background Medial temporal lobe epilepsy (MTLE) is associated with limbic atrophy involving the hippocampus, peri-hippocampal and extra-temporal structures. While MTLE is related to static structural limbic compromise, it is unknown whether the limbic system undergoes dynamic regional perfusion network alterations during seizures. In this study, we aimed to investigate state specific (i.e. ictal versus interictal) perfusional limbic networks in patients with MTLE. Methods We studied clinical information and single photon emission computed tomography (SPECT) images obtained with intravenous infusion of the radioactive tracer Technetium- Tc 99 m Hexamethylpropyleneamine Oxime (Tc-99 m HMPAO) during ictal and interictal state confirmed by video-electroencephalography (VEEG) in 20 patients with unilateral MTLE (12 left and 8 right MTLE). Pair-wise voxel-based analyses were used to define global changes in tracer between states. Regional tracer uptake was calculated and state specific adjacency matrices were constructed based on regional correlation of uptake across subjects. Graph theoretical measures were applied to investigate global and regional state specific network reconfigurations. Results A significant increase in tracer uptake was observed during the ictal state in the medial temporal region, cerebellum, thalamus, insula and putamen. From network analyses, we observed a relative decreased correlation between the epileptogenic temporal region and remaining cortex during the interictal state, followed by a surge of cross-correlated perfusion in epileptogenic temporal-limbic structures during a seizure, corresponding to local network integration. Conclusions These results suggest that MTLE is associated with a state specific perfusion and possibly functional organization consisting of a surge of limbic cross-correlated tracer uptake during a seizure, with a relative disconnection of the epileptogenic temporal lobe in the interictal period. This pattern of state specific shift in metabolic networks in MTLE may improve the understanding of epileptogenesis and neuropsychological impairments associated with MTLE.

PURPOSE To determine the diagnostic performance of In-111 capromab pendetide single photon emission computed tomography/computed tomography (SPECT/CT), in the prostate gland, seminal vesicles, and lymph nodes via correlation to a gold standard of histopathology. MATERIALS AND METHODS In this study, we retrospectively reviewed all In-111 capromab pendetide SPECT/CT acquired at our institution for dedicated histopathology within a 4-month period. Statistical measures of performance were calculated in terms of glandular, seminal vesicle, and lymph node activity. The accuracies of glandular and seminal vesicle activity were then correlated to the indices of risk, including the stage, Gleason score, and prostate-specific antigen level, as well as the treatment history. RESULTS Of the 200 scans meeting the criteria of our study, 197 had prostate gland histopathology, 94 had bilateral seminal vesicle histopathology, and 5 had a total of 43 resected lymph nodes for comparison. The overall accuracies of the scan results were determined to be 77.7% (area under the receiver operating characteristic curve [AUC] = 0.539) for the gland, 67.0% (AUC = 0.510) for the seminal vesicles, and 93.0% (AUC = 0.787) for lymph nodes. For glandular activity alone, scan accuracy was found to significantly improve with increasing Gleason score (P < 0.0001), and in a setting prior to treatment (P = 0.0005). No statistically significant differences were found between different scan groups with regards to seminal vesicle activity. CONCLUSIONS The results of this study provide substantiating evidence In-111 capromab pendetide can be used to accurately diagnose lymph node metastases from primary cancers of the prostate; however, they also suggest the test may have limited utility in diagnosing tumors within the prostate gland and seminal vesicles.

An arithmetic procedure was developed to determine the radioactivity required for an attenuation-correction transmission source for the delivery of a predetermined patient radiation dose for various patient-source configurations. The procedure determines the absorbed energy per incident photon from a chosen transmission radionuclide, based on Monte Carlo data. Results were verified using TLD and ionization chamber measurements. The method is useful in calculating the transmission source radioactivity for transmission computed tomography using a two-dimensional transmission source.

The effect of exametazime concentration, storage time, and the volume of the radiolabeling compound on the radiochemical purity of labeled exametazime doses was studied. Exametazime cold unit doses (CUDs) of 0.50, 0.33, 0.25, 0.17, and 0.13 mg/mL were prepared by reconstituting exametazime kits with 0.9% sodium chloride injection. After either one or two days of storage at -10 degrees C, four CUDs of each concentration were labeled with 0.2-0.3 mL of sodium pertechnetate Tc 99m (10-20 mCi). The radiochemical purity of CUDs was evaluated 15 minutes later by instant thin-layer chromatography. In a second experiment, exametazime CUDs of 0.5 mg/mL were prepared. After 0-19 days of storage at -10 degrees C, four CUDs were each labeled with 0.2 mL of sodium pertechnetate Tc 99m (10-20 mCi), and radiochemical purity was measured after 15 minutes. In a third experiment, exametazime CUDs of 0.5 mg/mL were labeled with 2.0 mL of sodium pertechnetate Tc 99m (10-20 mCi) after zero to five days of storage at -10 degrees C. The mean radiochemical purity was unacceptably low (less than 80%) for exametazime CUDs of 0.33, 0.25, 0.17, and 0.13 mg/mL; the 0.5-mg/mL CUDs were acceptably stable. Purity was less than 80% for CUDs stored for more than two days. The radiochemical purity of CUDs labeled with 2.0 mL of sodium pertechnetate Tc 99m was significantly greater than the purity of CUDs labeled with 0.2 mL for storage times exceeding two days.(ABSTRACT TRUNCATED AT 250 WORDS)

The Japanese Ministry of Health and Welfare guidelines (JMHWG) are currently the standard used to diagnose cardiac sarcoidosis. JMHWG incorporate (67)Gallium scintigraphy as a minor criterion, while fasting (18)fluorine-2-fluoro-2-deoxy-D-glucose (FDG) PET is not included. As there is no published data comparing the accuracy of prolonged fasting FDG PET-CT (PF-PET) and Gallium scintigraphy for detecting active cardiac sarcoidosis, we sought to compare these two modalities.We retrospectively reviewed medical records and nuclear images of 76 patients with suspected cardiac sarcoid who had either PF-PET or Gallium scintigraphy between January 2004 and August 2008. Eleven patients were excluded due to inadequate fasting for PF-PET, incomplete records or diagnosis other than sarcoid. Cardiac catheterizations, electrocardiogram interpretations, echocardiography reports, pathology reports, therapeutic interventions, and follow-up findings were correlated to PF-PET and Gallium scintigraphy results. Nuclear images of all patients including controls were reviewed independently by two experienced nuclear physicians blinded to results. Using JMHWG as reference standard, sensitivity, specificity, and accuracy of PF-PET were 85%, 90%, and 86.7% and for Gallium scintigraphy were 15%, 80%, and 42.8%.Relative to Gallium scintigraphy, PF-PET appears to provide greater accuracy for detecting cardiac sarcoidosis. Our findings also highlight the importance of revising JMHWG to incorporate PF-PET and the importance of adequate prolonged fasting prior to FDG PET imaging.

Coronary artery disease is frequently present in patients undergoing evaluation for reconstructive peripheral vascular surgery. Dobutamine-thallium imaging has been shown to be a reliable and sensitive noninvasive method for the detection of significant coronary artery disease. Eighty-seven candidates for vascular reconstruction underwent dobutamine-thallium imaging. Forty-eight patients had an abnormal dobutamine-thallium scan. Twenty-two patients had infarct only, while 26 had reversible ischemia demonstrated on dobutamine-thallium imaging. Fourteen of 26 patients with reversible ischemia underwent cardiac catheterization and 11 showed significant coronary artery disease. Seven patients underwent preoperative coronary artery bypass grafting or angioplasty. There were no postoperative myocardial events in this group. Three patients were denied surgery on the basis of unreconstructible coronary artery disease, and one patient refused further intervention. Ten patients with reversible myocardial ischemia on dobutamine-thallium imaging underwent vascular surgical reconstruction without coronary revascularization and suffered a 40% incidence of postoperative myocardial ischemic events. Five patients were denied surgery because of presumed significant coronary artery disease on the basis of the dobutamine-thallium imaging and clinical evaluation alone. Thirty-nine patients with normal dobutamine-thallium scans underwent vascular reconstructive surgery with a 5% incidence of postoperative myocardial ischemia. Dobutamine-thallium imaging is a sensitive and reliable screening method which identifies those patients with coronary artery disease who are at high risk for perioperative myocardial ischemia following peripheral vascular surgery.

Relative regional brain blood flow was measured in 23 clinically depressed adults by using ECD SPECT at baseline and again during actual prefrontal transcranial magnetic stimulation (TMS) following 5 daily sessions of TMS. TMS over prefrontal cortex caused increased activity in cortex directly under the stimulation (inversely correlated with distance from scalp to cortex) and decreased activity in remote regions (anterior cingulate and anterior temporal poles). High-frequency rTMS (20 Hz) caused more relative flow immediately below the TMS coil than did low-frequency rTMS (5 Hz). Confirming the hypotheses tested, repeated daily TMS over the prefrontal cortex in medication-free depressed adults appears to change both local and remote blood flow in a manner that may also depend on the frequency of stimulation and coil to outer cortex distance.

A 56-YEAR-OLD woman with a history of medullary thyroid carcinoma had a total thyroidectomy in 1968 with subsequent bilateral neck irradiation and then a right neck dissection in 1970. For recurrent disease, a left neck dissection was required in 1975, followed by a right supraclavicular and upper mediastinal dissection in 1980 with consequent lower neck and superior mediastinal irradiation. An octreotide study was performed in efforts to localize recurrent or metastatic medullary thyroid carcinoma. Abnormal uptake just to the right of the skull vertex and within the base of the skull and in the neck in the region of the thyroid gland (Fig 1) was found. Magnetic resonance imaging scan of the brain showed an extra-axial 1.2-cm mass along the fight parietal parasagittal convexity which enhanced uniformly, highly suggestive of a meningioma or possibly a metastases from the patient's known thyroid carcinoma (Fig 2). Magnetic resonance imaging scan of the neck showed a highly vascular right parapharyngeal mass extending from the carotid bifurcation encompassing the fight internal carotid artery with extension into the skull base. On two separate occasions, the parapharyngeal tumor was embolized with Ivalon particles in efforts to reduce its vascularity, before surgical removal. The patient underwent fight neck exploration with excision of the parapharyngeal mass. Pathology confirmed recurrence of medullary carcinoma of the thyroid. A few months later, the right extra-axial mass was surgically removed with pathological confirmation of a secretory meningioma. amine precursor uptake and decarboxylation (APUD) or neuroendocrine tumors have been shown to have an affinity for octreotide and have been described in recent literature. 4 The prime utility for octreotide has been endocrine active tumors of the gastroenteropancreatic system, malignant lymphomas, small cell lung carcinomas, pheochromocytomas, and carcinoid tumors. The complete list however is becoming quite extensive) Both endocrine and nonendocrine neck and cranial tumors are included in the differential for octreotide uptake. Detection for meningiomas by octreotide scanning has shown a 100% sensitivity: -7 Medullary carcinoma of the thyroid has shown a 71% sensitivity for the presence of somatostatin receptors in a recent series. Possible causes of head and neck activity on octreotide scans include the following

Monoclonal antibodies have been raised against Ama isolated from human and experimental atherosclerotic plaque. 131I-Ama-MoAb in the whole antibody form was injected into normal NZW rabbits and Watanabe hyperlipidemic rabbits. Biodistribution studies showed that atheromatous aortas had a significantly higher (5-7X) uptake of 131I-Ama-MoAb than that of normal aortas. However, 131I-Ama-MoAb was cleared very slowly from atherosclerotic rabbits. As a result, atheromas could not be identified by imaging because of the low target to non-target ratios.

Teleradiology increases the ability of radiologists to provide service to remote and underserved locations as well as coverage at times when direct reading of images is not possible. Good practices for teleradiology are described in the American College of Radiology (ACR) teleradiology standard. Teleradiology equipment is converging with picture archiving and communications systems (PACS) equipment so that diagnostic interpretation from remote locations is possible. Image capture can be directly from digital modalities or by film scanner. Transmission speed is still an issue. High transmission speeds were difficult to achieve but recent improvements may increase speeds and decrease costs.

The incidence of osteoporosis and fractures of the hip are diminished in blacks and in obese subjects. To determine whether bone mass is increased in them, bone mineral density (BMD) of the lumbar spine, trochanter, and femoral neck was measured by dual photon absorptiometry in 89 nonobese white and 51 nonobese black women, all of whom were within 30% of their ideal body weight and between the ages of 20 and 50 yr, and in 21 obese white women and 21 obese black women, all of whom weighed 30% on more than their ideal body weight and were in the same age range. The BMD of the mid radius was also measured by single photon absorptiometry. The mean BMD of the mid radius was higher in black than in white nonobese women [0.73 +/- 0.01 (+/- SE) vs. 0.70 +/- 0.01 g/cm2; P less than 0.01] and was not altered by obesity in either group. The mean BMD was higher in the black than in the white nonobese women at the lumbar spine (1.23 +/- 0.02 vs. 1.16 +/- 0.01 g/cm2; P less than 0.01), trochanter (0.78 +/- 0.02 vs. 0.72 +/- 0.01 g/cm2; P less than 0.01) and femoral neck (0.96 +/- 0.02 vs 0.90 +/- 0.02 g/cm2; P less than 0.02). The mean body weight was higher in the obese than in the nonobese white women (92 +/- 2 vs. 61 +/- 1 kg; P less than 0.001) and black women (94 +/- 3 vs. 63 +/- 1 kg; P less than 0.001). The mean BMD was higher in the obese than in the nonobese white women at the lumbar spine (1.24 +/- 0.03 g/cm2; P less than 0.05), trochanter (0.89 +/- 0.04; P less than 0.001), and femoral neck (0.99 +/- 0.03; P less than 0.01) and was higher in the obese than in the nonobese black women at the lumbar spine (1.33 +/- 0.03 g/cm2; P less tham 0.01), trochanter (0.88 +/- 0.04 g/cm2; P less than 0.05), and femoral neck (1.04 +/- 0.03 g/cm2; P less than 0.05). Multivariate regression analysis revealed positive correlations between body weight and BMD at each of the 3 weight-bearing sites, but not at the mid radius, in both the black women and white women.(ABSTRACT TRUNCATED AT 400 WORDS)

Factors that influence hemoglobin (Hb)A(Ic) synthesis by intact erythrocytes were studied in vitro. After incubation cells were lysed, and hemoglobins were separated by isoelectric focusing on polyacrylamide slab gels and quantitated by microdensitometry. HbA(Ic) increased with time, glucose concentrations (5-500 mM), and incubation temperature (4 degrees -37 degrees C). Low temperatures allowed prolonged incubations with minimal hemolysis. At 4 degrees C HbA(Ic) increased linearly with time for 6 wk; after incubation at the highest glucose concentration, HbA(Ic) comprised 50% of total hemoglobin. Insulin (1 and 0.1 mU/ml) did not affect HbA(Ic) synthesis in vitro. In addition to glucose, galactose and mannose, but not fructose, served as precursors to HbA(Ic). A good substrate for hexokinase (2-deoxyglucose) and a poor hexokinase substrate (3-O-methylglucose), were better precursors for HbA(Ic) synthesis than glucose, suggesting that enzymatic phosphorylation of glucose is not required for HbA(Ic) synthesis. Autoradiography after erythrocyte incubation with (32)P-phosphate showed incorporation of radioactivity into HbA(Ia1) and A(Ia2), but not HbA(Ib), A(Ic), or A. Acetylated HbA, generated during incubation with acetylsalicylate, migrated anodal to HbA(Ic) and clearly separated from it. Erythrocytes from patients with insulinopenic diabetes mellitus synthesized HbA(Ic) at the same rate as controls when incubated with identical glucose concentrations. Likewise, the rate of HbA(Ic) synthesis by erythrocytes from patients with cystic fibrosis and congenital spherocytosis paralleled controls. When erythrocytes from cord blood and from HbC and sickle cell anemia patients were incubated with elevated concentrations of glucose, fetal Hb, HbC, and sickle Hb decreased, whereas hemoglobins focusing at isoelectric points near those expected for the corresponding glycosylated derivatives appeared in proportionately increased amounts.

Because leukotrienes and prostaglandins are inflammatory mediators derived from arachidonic acid, their potential role in oleic acid-induced lung injury was evaluated in control and in essential fatty acid-deficient (EFAD) rats depleted of arachidonic acid substrate. In control rats, oleic acid (0.06 ml/kg iv) increased the pulmonary permeability index (measured by scintigraphy) from -10 +/- 13 x 10(-6) s-1 to 217 +/- 20 x 10(-6) s-1 and 118 +/- 13 x 10(-6) s-1 at 5 and 50 min (P less than 0.05), respectively. It also caused arterial hypoxemia at 30 min (P less than 0.05). Compared with saline controls, oleic acid increased bronchoalveolar lavage fluid levels of immunoreactive (i) LTC4/D4, iLTB4, (P less than 0.01), and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) (P less than 0.05). In EFAD rats, oleic acid failed to significantly increase the lung permeability index at 5 and 50 min. In contrast to control rats, oleic acid failed to cause hypoxemia in the EFAD rats. Bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha after oleic acid in EFAD rats were lower compared with oleic acid controls, whereas iLTC4/D4 in the oleic acid EFAD group was not decreased. Treatment with intraperitoneal ethyl arachidonate (400 mg over 2 wk) reversed the resistance of EFAD rats such that the pulmonary edema (P less than 0.05) was evident after oleic acid. This latter group also manifested a significant (P less than 0.05) rise in the bronchoalveolar lavage levels of iLTB4 and i6-keto-PGF1 alpha. These results suggest that arachidonic acid metabolites contribute to oleic acid-induced pulmonary permeability.

During Tc-99m medronate (MDP) bone scintigraphy, visualization of the synovium during blood flow and blood pool phases was present in a patient with septic arthritis of the left knee. Inflammation with hyperemia of the synovium was the cause for radionuclide localization, which was enhanced by the large photon-deficient effusion distending the suprapatellar bursa. The synovium was not seen on delayed images after redistribution of the radionuclide from blood pool to bone phase.

Following spinal cord injury in rats there was a time-dependent change of vascular permeability as reflected by extravasation of 125I-labelled serum albumin. The change of vascular permeability correlated with tissue calcium and water accumulation suggesting that cord exposure to plasma calcium as a consequence of vascular injury may contribute to the progressive post-traumatic cord necrosis.

Scintigraphy with Tc-99m labeled red blood cells (RBCs) was used to evaluate a patient with a large cutaneous hemangioma. The usefulness of this procedure when combined with arteriography is discussed.

Thromboxane-prostacyclin imbalance may be an important determinant of platelet-vessel wall interactions that are vital in circulatory homeostasis. In experimental spinal cord injury, the vascular damage contributes substantially to the process of progressive secondary injury culminating in post-traumatic myelopathy. In this study, we found a time-dependent alteration of thromboxane-prostacyclin balance in the injured spinal cord with thromboxane dominance during the first 2 h: a time when maximal vascular injury is reflected by extravasation of 125I-labelled serum albumin. The thromboxane-prostacyclin imbalance reverted to favor prostacyclin by 18 h post-injury. This time-dependent alteration of thromboxane-prostacyclin balance should be considered in the planning of therapeutic attempts to prevent secondary injury by pharmacological modulation of platelet-vessel wall interaction.

The role of arachidonic acid metabolites in oleic acid-induced lung injury in anesthetized dogs was investigated. Oleic acid was administered as a bolus injection into the pulmonary artery in the following dose sequence: 0.05, 0.10, and 0.20 ml/kg at 30, 60, and 120 min, respectively, after either indomethacin (10 mg/kg iv) or vehicle. A control group (n = 3) received normal saline instead of oleic acid. Measurements of hemodynamic parameters, mean systemic (MAP), pulmonary capillary wedge, and pulmonary artery pressures (PAP), cardiac output, arterial blood gases, extravascular lung waters (EVLW) by thermaldye double indicator dilution techniques and plasma immunoreactive thromboxane B2 (iT×B2), by radioimmunoassay were obtained at zero time (baseline) and 20 min following each oleic acid injection. A new noninvasive technique was employed to measure pulmonary capillary protein leak by the scintigraphic analysis of intravenously administered technetium-99m radiolabeled human serum albumin (99mTc-HSA) in the cardiac and lung regions. Oleic acid injection caused a significant dose related fall in MAP (P < 0.0002), arterial pO2 (P < 0.0001), and cardiac output (P < 0.001), and increases in EVLW (P < 0.003) and plasma iT×B2 (P < 0.02) in the vehicle pretreated animals, while mean PAP remained unchanged. In contrast, in the indomethacin pretreated dogs, MAP, EVLW, cardiac output, and plasma iT×B2 levels did not change from baseline values and there was an increase in mean PAP. Pulmonary vascular resistance was significantly elevated (P < 0.05) in both groups. Compared to the control group, significant pulmonary capillary protein leaks occurred at the 0.10 (P < 0.05) and 0.20 (P < 0.01) ml/kg oleic acid doses in the vehicle pretreated dogs. Indomethacin failed to prevent the pulmonary capillary protein leak. There was a significant (P < 0.02) correlation (r = 0.72) observed between plasma iT×B2 levels and maximal percentage protein leaks for the combined indomethacin and vehicle pretreated dogs. It was concluded that thromboxanes may serve as markers of oleic acid-induced lung injury but do not appear to mediate the resultant changes in pulmonary microvascular permeability.