Elevated Serum IgG4 Complicated by Pericardial Involvement with a Patchy (18)F-FDG Uptake in PET/CT: Atypical Presentation of IgG4-related Disease.

IgG4-related pericardial involvement has rarely been reported and its clinical features remain unknown. We herein report a case of a 50-year-old woman with pericarditis who presented with a fever, elevated C-reactive protein levels, elevated serum IgG4 concentrations, and thickened pericardium with a patchy (18)F-fluorodeoxyglucose (FDG) uptake. A biopsy specimen of (18)F-FDG accumulated in the mediastinal lymph nodes revealed an abundant infiltration of IgG4-bearing plasma cells without fibrosis. Moderate-dose glucocorticoids promptly resolved the physical, serological, and imaging abnormalities, thus indicating a relatively acute and reversible nature of IgG4-related pericardial involvement.

Toward in vivo imaging of heart disease using a radiolabeled single-chain Fv fragment targeting tenascin-C.

Antibodies specific to a particular target molecule can be used as analytical reagents, not only for in vitro immunoassays but also for noninvasive in vivo imaging, e.g., immunoscintigraphies. In the latter case, it is important to reduce the size of antibody molecules in order to achieve suitable in vivo "diagnostic kinetics" and generate higher-resolution images. For these purposes, single-chain Fv fragments (scFvs; M(r) < 30 kDa) have greater potential than intact immunoglobulins (~150 kDa) or Fab (or Fab') fragments (~50 kDa). Our recent observation of enhanced tenascin-C (Tnc) expression at sites of cardiac repair after myocardial infarction prompted us to develop a radiolabeled scFv against Tnc for in vivo imaging of heart disease. We cloned the genes encoding the heavy and light chain variable domains of the mouse anti-Tnc monoclonal antibody 4F10, and combined them to create a single gene. The resulting scFv-4F10 gene was expressed in E. coli cells to produce soluble scFv proteins. scFv-4F10 has an affinity for Tnc (K(a) = 3.5 × 10(7) M(-1)), similar to the Fab fragment of antibody 4F10 (K(a) = 1.3 × 10(7) M(-1)) and high enough to be of practical use. A cysteine residue was then added to the C-terminus to achieve site-specific (111)In labeling via a chelating group. The resulting (111)In-labeled scFv was administered to a rat model of acute myocardial infarction. Biodistribution and quantitative autoradiographic studies indicated higher uptake of the radioactivity at the infarcted myocardium than the noninfarcted one. Single photon emission computed tomography (SPECT) provided in vivo cardiac images that coincided with the ex vivo observations. Our results will promote advances in diagnostic strategies for heart disease.

Noninvasive detection of cardiac repair after acute myocardial infarction in rats by 111 In Fab fragment of monoclonal antibody specific for tenascin-C.

Left ventricular (LV) remodeling after acute myocardial infarction (MI) causes heart failure, and thus it is important to evaluate cardiac repair as the early stage of LV remodeling. Tenascin-C (TNC), an extracellular matrix glycoprotein, is transiently and abundantly expressed in the heart during the early stage of tissue remodeling after MI. However, it is not expressed in healthy adult heart. This study was undertaken to develop a new noninvasive diagnostic technique to detect cardiac repair after acute MI using 111 In Fab fragment of a monoclonal antibody specific for TNC. 111 In-anti-TNC-Fab was injected intravenously in 13 rats at 1 (D1, n = 3), 3 (D3, n = 5), and 5 (D5, n = 5) days after producing MI and in 5 sham-operated rats (S). We performed autoradiography and dual-isotope single-photon emission computed tomography imaging (SPECT) of 111 In-anti-TNC-Fab and 99mTc methoxyisobutyl isonitrile (MIBI). The radioactivity in the heart was significantly higher in D (D1, 0.45 +/- 0.06% injected-dose/g; D3, 0.64 +/- 0.12; D5, 0.38 +/- 0.07) than S (0.27 +/- 0.06, P < 0.01 versus D1 and D3, P < 0.05 versus D5). By autoradiography, higher radioactivities were observed in the infarcted area than in the noninfarcted area of MI hearts. Dual-isotope SPECT demonstrated the regional myocardial uptake of 111 In-anti-TNC-Fab, which was complementary to the perfusion image. The results of the present study indicated that we can localize the infarcted region in the heart by ex vivo and in vivo imaging methods using 111 In-anti-TNC-Fab, and suggested the potential usefulness of noninvasive detection of cardiac repair.

PET study of brain acetylcholinesterase in cerebellar degenerative disorders.

To elucidate characteristic changes of brain acetylcholinesterase (AChE) in cerebellar degenerative disorders. Eight patients with the cerebellar variant of multiple system atrophy (MSA-C), 7 patients with spinocerebellar ataxia type-3 (SCA-3), 3 patients with SCA-6, and 13 healthy age-matched volunteers participated in this study. Brain AChE activity was measured by [(11)C] N-methylpiperidin-4-yl propionate PET in all subjects. Brain AChE activities were significantly decreased in the thalamus (-27%) and the posterior lobe of cerebellar cortex (-36%) in patients with MSA-C and in the thalamus (-23%) in patients with SCA-3 compared with healthy controls (P < 0.01). Thalamic AChE activities of SCA-3 patients were negatively correlated with the unified Parkinson's disease rating scale motor subscore (P < 0.001). AChE activities were not significantly altered in the cerebral cortex in any disease group. Reduction of AChE activities in the thalamus and cerebellum in MSA and in the thalamus in SCA-3 suggest that cholinergic modulating drugs may have a role in the treatment of ataxia and other symptoms in these disorders.

Development and performance evaluation of the second model 256-detector row CT.

Since our initial development of the 256-detector row CT scanner (256-row CT) for four-dimensional (4D) imaging of moving organs in 2003, the results of physical performance and those in animal and human studies have suggested that this scanner may be useful in the examination of moving organs such as the heart and lungs. We have now developed a second model of the 256-row CT with improved specifications, with a scan time of 0.5 s/rotation at the highest speed and real-time reconstruction and display of dynamic 3D images (4D images). Here, we investigated the image characteristics of the new model, including spatial resolution, noise, and low-contrast detectability, as well as the dose profile and its integral in stationary phantoms. One volunteer and one patient with lung cancer were scanned, and their images were evaluated. The results show that all characteristics have been improved compared with those of the first model, with a remarkable improvement in the low-contrast detectability and slice sensitivity profile. In a contrast study, coronary arteries were clearly visualized in the normal heart without electrocardiographic gating. Movement and deformation of the tumor in the patient with lung cancer was captured in a study of a single breath cycle. The second model 256-row CT with improved characteristics may be beneficial in imaging of moving organs such as the heart and lungs, and may enable cerebral perfusion studies of the whole brain.

Altered brain activation by a false recognition task in young abstinent patients with alcohol dependence.

BACKGROUND: Heavy alcohol intake induces both structural and functional changes in the central nervous system. Recent research developments converged on the idea that even in patients with alcohol dependence without apparent structural brain changes, some cognitive impairment exists, and associated functional change could be visualized by neuroimaging techniques. However, these data were from old (more than 50 years) patients using working memory and response inhibition tasks. Whether young abstinent patients show aberrant signs of brain activation is a matter of interest, specifically by the long-term memory retrieval task. METHODS: Subjects were 9 young patients with alcohol dependence with long-term abstinent (8 males and 1 female) and age- and education-matched 9 healthy controls (7 males and 2 females). We used a modified false recognition task in a functional MRI study. RESULTS: The young patients with alcohol dependence showed reduced activation in the right dorsolateral prefrontal cortex, anterior cingulate cortex (ACC), left pulvinar in the thalamus, and in the right ventral striatum, although behavioral performances and regional patterns of brain activation were similar between patients and controls. CONCLUSIONS: Long-term memory retrieval induced altered activations in prefrontal lobes, ACC, thalamus, and ventral striatum in young patients with alcohol dependence. These findings were correspondent to deficits of goal directed behavior, monitoring the erroneous responses, memory function, and drug-seeking behavior. Furthermore, these reduced activations can be considered as latent "lesions," suggesting subclinical pathology in alcoholic brains.

Tricolored "tricolore" myocardium by selective intracoronary injection of contrast using 256-slice cone-beam computed tomography.

We report our experience with 256-slice cone-beam computed tomography following selective coronary arterial bolus injection in pigs, which distinguished the segmented left ventricular (LV) myocardium supplied by each coronary artery into three parts more clearly than with other modalities. Two pigs were anesthetized and catheters positioned in the left anterior descending branch (LAD) of the coronary artery in pig 1 and the left circumflex branch (LCx) in pig 2. 10 ml of iodinated contrast material diluted with 40 ml of saline was injected at a rate of 3 ml/s. Entire heart scanning was started simultaneously and continued for 25 s. We selected the most static images of the LV at around 5 s after contrast injection. Axial source and multiplanar reconstruction images from the right anterior oblique projection clearly revealed tricolored, segmented LV myocardial enhancement of the anterior and apical walls and inter-ventricular septum in pig 1, and the lateral and posterior walls in pig 2. We were able to identify the borders between the LV myocardium supplied by the LAD, the LCx and the right coronary artery, respectively, and this technique may facilitate new cardiovascular diagnoses.

Preliminary study: color map of hepatocellular carcinoma using dynamic contrast-enhanced 256-detector row CT.

To distinguish hepatocellular carcinoma (HCC) from normal liver tissue, a color map was made by dynamic contrast-enhanced 256-detector row CT developed at our institute. Dynamic enhanced CT of the liver of three patients with HCC was studied. The CT has 912 (transverse) x 256 (cranio-caudal) elements, each measuring approximately 0.5 mm x 0.5mm at the center of rotation. Scanning for 10 s (1.0 s/rotation) was started 30 s after intravenous injection of contrast medium. The reconstruction increment was 0.62 mm with a time interval of 0.1s and a matrix size of 512 x 512 x 256. Color maps were generated to show the gradient of the regression line of the time-density change. Due to volume acquisition, the 3D color map can be created using continuous 10-s scanning. The densities of the HCC and liver were decreased and increased during scanning, respectively. The HCC was detected clearly in the color map as a downward-sloping region. Dynamic enhanced 256-detector row CT could be useful for detecting malignant tumors in the liver with a short scan time.

Cardiac imaging using 256-detector row four-dimensional CT: preliminary clinical report.

PURPOSE: Along with the increase of detector rows on the z-axis and a faster gantry rotation speed, the spatial and temporal resolutions of the multislice computed tomography (CT) have been improved for noninvasive coronary artery imaging. We investigated the feasibility of the second specification prototype 256-detector row four-dimensional CT for assessing coronary artery and cardiac function. MATERIALS AND METHODS: The subjects were five patients with coronary artery disease. Contrast medium (40-60 ml) was intravenously administered at the rate of 3-4 ml/s. The patient's whole heart was scanned for 1.5 s to cover at least one cardiac cycle during breathholding without electrocardiographic gating. Parameters used were 0.5 mm slice thickness, 0.5 s/rotation, 120 Kv, and 350 mA, with a half-scan reconstruction algorithm (temporal resolution 250 ms). Twenty-six transaxial datasets were reconstructed at intervals of 50 ms. RESULTS: The assessability of the coronary arteries in AHA segments 1, 2, 3, 5, 6, 7, 9, and 11 was visually evaluated, resulting in 29 of 32 (90.9%) segments being assessable. Functional assessment was also performed using animated movies without banding artifacts in all cases. CONCLUSIONS: The 256-detector row four-dimensional CT can assess the coronary artery and cardiac function using data during 1.5 s without banding artifacts.

Superiority of synchrony of 256-slice cone beam computed tomography for acquiring pulsating objects. Comparison with conventional multislice computed tomography.

PURPOSE: A prototype 256-slice cone beam computed tomography (CT) provides complete volumetric data within a single gantry rotation (1 s/rotation) with 0.5 mm slice-thickness. MATERIALS AND METHODS: Calcified phantoms (200-400 HU) were attached to the balloon of a pulsating phantom and moved at a rate of 5-90/min. Acquisition was performed during one to-and-fro motion at each pulsation rate without electrocardiogram (ECG)-gating. Each period was divided into 10 phases, and compared to conventional multislice CT scanning without ECG-gating. RESULTS: At 5-20/min, the configuration of calcified phantoms continued to the through-plane without gaps. At 60/min, duplicated calcified phantoms at end-systole and end-diastole were observed without motion. At 90/min, motion could be observed without gaps but was more blurred, and total calcified volume, Agatston scores, mean and max CT values of three phantoms were almost equal compared with those at static state. However, at 60/min, total calcified volume, scores, mean and max CT values of three phantoms were decreased to 64%, 37%, 80% and 56%, respectively, compared with those at static state. In multislice CT, even at lower rates, there were gaps in the through-plane. At 60/min, total calcified volume, scores, mean and max CT values of three phantoms were decreased to only 8%, 3%, 79% and 53%, respectively, compared with static state. CONCLUSION: This new prototype's unique character (synchrony) enables the acquisition of pulsating objects. These can be acquired without gaps in the through-plane even in the absence of ECG-gating. However, its present temporal resolution only permits accurate quantitative evaluation of calcium up to 20/min.

Molecular therapy of human neuroblastoma cells using Auger electrons of 111In-labeled N-myc antisense oligonucleotides.

UNLABELLED: Auger electrons can create breaks in nucleic acids, giving them possible therapeutic utility. We investigated the therapeutic effect of Auger electrons emitted by 111In-labeled phosphorothioate antisense oligonucleotides on human neuroblastoma cells in which N-myc was overexpressed. METHODS: Human SK-N-DZ neuroblastoma cells (5 x 10(6) cells) were treated with cationic reverse-phase evaporation vesicles (REVs) encapsulating 111In-labeled antisense (40 MBq/2 nmol of oligonucleotides/mumol of total phospholipids) that had an average diameter of 250 nm. Hybridization of the radiolabeled oligonucleotides with N-myc messenger RNA (mRNA), N-myc expression, and cell proliferation were investigated. The tumorigenicity of treated cells was analyzed in nude mice. Nonradiolabeled antisense, 111In-labeled sense, or empty cationic REVs were used as controls. RESULTS: 111In-Labeled antisense, which hybridized with N-myc mRNA, was detected in cells at 12 and 24 h after the initiation of treatment. Reduced N-myc expression and inhibited cell proliferation were shown in the same cells at 48 h after the completion of treatment. N-myc expression-suppressed cells produced intraperitoneal tumors in nude mice, but the average weight of the tumors was lower than that of tumors in control mice. CONCLUSION: Auger electrons emitted from 111In in close proximity to their target N-myc mRNA may prolong the time to cell proliferation in human neuroblastoma cells due to inhibition of the translation of N-myc. Auger electron therapy therefore has potential as an internally delivered molecular radiotherapy targeting the mRNA of a tumor cell.

Physical evaluation of the weighted Feldkamp algorithms applied to the 256-detector row CT scanner for volumetric cine imaging.

RATIONALE AND OBJECTIVES: To improve effective scan time and image quality in cone-beam computed tomography (CT), Parker's weighting function (half scan [HS]-Feldkamp-Davis-Kress [FDK]) extended to a larger range up to 2pi was proposed as new half-scan algorithm (NHS-FDK). We conducted a practical physical evaluation of NHS-FDK and HS-FDK using 256-detector row CT. MATERIALS AND METHODS: Three types of weighting function (full-scan [FS-FDK], HS-FDK, and NHS-FDK) were evaluated by using 256-detector row CT for five variables, ie, point spread function, image noise, CT number uniformity, Feldkamp artifact, temporal resolution, and clinical evaluation. RESULTS: Image noise, Feldkamp artifact, and temporal resolution were dependent on weighting function. Image noise magnitude was independent of projection angle for all regions of interest with FS-FDK, but showed a symmetric pattern with projection angle with HS-FDK and NHS-FDK. With regard to temporal resolution, NHS-FDK did not remove the motion artifact in the heart except in such slower motion organs as the pulmonary vessels, whereas HS-FDK reduced the motion artifact in the heart. HS-FDK had an even more incomplete data region in the Radon space than FS-FDK, suggesting that it would provide poor image quality distant to the midplane in the longitudinal direction. In practical testing in human subjects, HS-FDK showed inferior performance in all variables except temporal resolution. CONCLUSION: Despite its inferiority to FS-FDK for static objects, HS-FDK may be useful in chest imaging. Contrary to previous findings using static images, NHS-FDK failed to show advantages over HS-FDK or FS-FDK in a moving phantom and human subjects.

A dose-finding study of duloxetine based on serotonin transporter occupancy.

RATIONALE: Positron emission tomography (PET) has been utilized for determining the dosage of antipsychotic drugs. To evaluate the dosage of antidepressants such as selective serotonin reuptake inhibitors, serotonin transporter occupancy (5-HTT) is also a useful index. OBJECTIVES: We investigated the degree of 5-HTT occupancy with different doses of the antidepressant duloxetine and the time-course of 5-HTT occupancy using PET. METHODS: PET scans with [11C]DASB were performed before and after a single administration of duloxetine (5-60 mg), and three consecutive scans were performed after a single dose or repeated doses of 60 mg of duloxetine. RESULTS: 5-HTT occupancies by duloxetine were increased by 35.3 to 86.5% with dose and plasma concentration increments. The ED50 value of 5-HTT occupancy was 7.9 mg for dose and 3.7 ng/ml for plasma concentration. In the time-course of 5-HTT occupancy, mean occupancies were 81.8% at 6 h, 71.9% at 25 h, and 44.9% at 53 h after a single administration, and 84.3% at 6 h, 71.9% at 49 h, and 47.1% at 78 h after repeated administrations. CONCLUSIONS: Based on 5-HTT occupancy, 40 mg and more of duloxetine was needed to attain 80% occupancy, and 60 mg of duloxetine could maintain a high level of 5-HTT occupancy with a once-a-day administration schedule.

Properties of the prototype 256-row (cone beam) CT scanner.

We evaluated Feldkamp artifacts, which are specific to cone-beam computed tomography (CT), in phantom and clinical studies using the 256-multidetector-row CT (256MDCT), and compared the reconstruction accuracy of axial and helical scans. Image noise, slice sensitivity profile (SSP) and artifacts with the 256MDCT were evaluated using a phantom, and the results were compared to those of a 64MDCT. We also examined chest and abdomen scans produced with the 256MDCT in volunteers. For the axial scan, Feldkamp artifacts were visualized as high-frequency streak-like artifacts that are oriented horizontally at the edge of the scan region in the phantom study. Similar results were obtained with the volunteers in soft-tissue regions near either bony structures or air pockets. Feldkamp artifacts with the 256MDCT can lead to misdiagnosis if not correctly identified and minimized via helical scanning. Image noise was less for axial than helical scans, while SSP was better with helical than axial scans. Feldkamp artifacts observed in the 256MDCT images, however, did not generally affect the interpretation of images. The 256MDCT promises more accurate diagnosis, and will provide volumetric cine images of wider cranio-caudal coverage, enabling new applications of CT.

Noise properties for three weighted Feldkamp algorithms using a 256-detecotor row CT-scanner: case study for hepatic volumetric cine imaging.

In cone-beam geometry, image quality may be degraded or artifacts may occur if the cone angle is substantially wide. This is because a cone-beam scan along a circular orbit does not collect the complete set of data required to make an exact reconstruction of all volumetric data. To increase temporal resolution and thus image quality in cone-beam geometry, Silver proposed the new half-scan algorithm (NHS-FDK), which extends Parker's weighting function (HS-FDK) by utilizing a larger range up to 2pi. Here, we evaluated these algorithms for hepatic contrast-enhanced CT in cine scan mode using a 256-detector row CT. The full-scan (FS-FDK) images show uniform distribution of the image noise and CT-number uniformity. Image noise and CT-number uniformity with HS-FDK and NHS-FDK images follow the initial projection angle. HS-FDK images therefore have more changeable higher intensity (brighter) and a lower intensity (darker) areas than respective FS-FDK and NHS-FDK images. We concluded that, considering the trade-off between image quality and temporal resolution, the NHS-FDK algorithm is useful in volumetric cine imaging for the abdomen.

Optimizing T2-weighted magnetic resonance sequences for surface coil microimaging of the eye with regard to lid, eyeball and head moving artifacts.

PURPOSE: To acquire high-resolution magnetic resonance (MR) images, we developed a new blinking artifact reduced pulse (BARP) sequence with a surface coil specialized for microscopic imaging (47 mm in diameter). MATERIALS AND METHODS: To reduce eye movement, we ascertained that the subjects' eyes were kept open and fixated to the target in the 1.5-T MR gantry. To reduce motion artifacts from blinking, we inserted rest periods for blinking (1.5 s within every 5 s) during MR scanning (T2-weighted fast spin echo; repetition time, 5 s; echo time, 100 ms; echo train, 11; matrix, 256 x 128; field of view, 5 cm; 1-mm thickness x 30 slices). Three scans (100 s x 3) were performed for each normal subject, and they were added together after automatic adjustment for location to reduce quality loss caused by head motion. RESULTS: T2-weighted MR images were acquired with a high resolution and a high signal-to-noise ratio. Motion artifacts were reduced with BARP, as compared with those with random blinking. Intraocular structures such as the iris and ciliary muscles were clearly visualized. Because the whole eye can be covered with a 1-mm thickness by this method, three-dimensional maps can easily be generated from the obtained images. CONCLUSION: The application of BARP with a surface coil of the human eye might become a useful and widely adopted procedure for MR microimaging.

Clinical potentials for dynamic contrast-enhanced hepatic volumetric cine imaging with the prototype 256-MDCT scanner.

OBJECTIVE: To achieve dynamic contrast-enhanced hepatic volumetric cine imaging, we developed a prototype 256-MDCT scanner. This study examined the feasibility of the technique for human hepatic imaging in three hepatocellular carcinoma patients. CONCLUSION: Volumetric cine imaging successfully visualized dynamic contrast enhancement of the hepatocellular carcinoma. It is helpful to evaluate the phase of contrast enhancement or for functional studies of the head, renal artery, coronary artery, and liver.

Functional network in the prefrontal cortex during episodic memory retrieval.

A recent consistent finding in neuroimaging studies of human memory is that the prefrontal cortex (PFC) is activated during episodic memory retrieval. To date, however, there has been no direct evidence to explain how activity in the right and left PFC and in the anterior and posterior PFC are functionally interconnected. The goal of the present study was to obtain such evidence by event-related functional magnetic resonance imaging (MRI) and the functional connectivity method. Subjects were first asked to try to remember a series of associate-word lists outside the MRI scanner in preparation for a later recognition test. In the MRI scanning phase, they were asked to make recognition judgments in regard to old words, semantically related lure words, and unrelated new words. The analysis of functional connectivity revealed that the posterior PFC in each hemisphere had strong functional interconnections with the contralateral posterior PFC, whereas the anterior PFC in each hemisphere had only weak functional interconnections with the contralateral anterior PFC. No strong functional interconnections were found between the anterior and posterior PFC in either hemisphere. These findings support the hypothesis of an associative contribution of the bilateral posterior PFC to episodic memory retrieval and a dissociative contribution of the bilateral anterior PFC.