Simulation study of a brain PET scanner using TOF-DOI detectors equipped with first interaction position detection.

Objective. The aim of this study is to evaluate the performance characteristics of a brain positron emission tomography (PET) scanner composed of four-layer independent read-out time-of-flight depth-of-interaction (TOF-DOI) detectors capable of first interaction position (FIP) detection, using Geant4 application for tomographic emission(GATE). This includes the spatial resolution, sensitivity, count rate capability, and reconstructed image quality.Approach. The proposed TOF-DOI PET detector comprises four layers of a 50 × 50 cerium-doped lutetium-yttrium oxyorthosilicate (LYSO:Ce) scintillator array with 1 mm pitch size, coupled to a 16 × 16 multi-pixel photon counter array with 3.0 mm × 3.0 mm photosensitive segments. Along the direction distant from the center field-of-view (FOV), the scintillator thickness of the four layers is 2.5, 3, 4, and 6 mm. The four layers were simulated with a 150 ps coincidence time resolution and the independent readout make the FIP detection capable. The spatial resolution and imaging performance were compared among the true-FIP, winner-takes-all (WTA) and front-layer FIP (FL-FIP) methods (FL-FIP selects the interaction position located on the front-most interaction layer in all the interaction layers). The National Electrical Manufacturers Association NU 2-2018 procedure was referred and modified to evaluate the performance of proposed scanner.Main results. In detector evaluation, the intrinsic spatial resolutions were 0.52 and 0.76 mm full width at half-maximum (FWHM) at 0° and 30° incidentγ-rays in the first layer pair, respectively. The reconstructed spatial resolution by the filter backprojection (FBP) achieved sub-millimeter FWHM on average over the whole FOV. The maximum true count rate was 207.6 kcps at 15 kBq ml-1and the noise equivalent count rate (NECR_2R) was 54.7 kcps at 6.0 kBq ml-1. Total sensitivity was 45.2 cps kBq-1and 48.4 cps kBq-1at the center and 10 cm off-center FOV, respectively. The TOF and DOI reconstructions significantly improved the image quality in the phantom studies. Moreover, the FL-FIP outperformed the conventional WTA method in terms of the spatial resolution and image quality.Significance. The proposed brain PET scanner could achieve sub-millimeter spatial resolution and high image quality with TOF and DOI reconstruction, which is meaningful to the clinical oncology research. Meanwhile, the comparison among the three positioning methods indicated that the FL-FIP decreased the image degradation caused by Compton scatter more than WTA.

Simulation study of potential time-of-flight capabilities for a multilayer DOI-PET detector with an independent readout structure.

A multilayer depth-of-interaction positron emission tomography (DOI-PET) detector with an independent readout structure has a potential advantage as a time-of-flight (TOF)-PET detector. The thin scintillator block of each detector layer can afford an improved coincidence time resolution (CTR) of ∼100 ps because the photon transfer time spread within the scintillator inherently decreases. To evaluate the potential TOF capabilities of a multilayer DOI-PET detector, which consists of thin layers of a cerium-doped lutetium-yttrium oxyorthosilicate (LYSO:Ce) scintillator coupled to a multi-pixel photon counter (MPPC) array, we examined the detector's CTR performance via Monte Carlo simulations. We used several types of scintillator structures: a monolithic plate, laser-processing array with 3.2 mm pitch, fine laser-processing array with 1.6 mm pitch, and pixelated array with 3.2 mm pitch, with 2, 4, 6, and 8 mm thickness values of a 25.6 mm × 25.6 mm scintillator cross-section. The MPPC array was composed of 3.0 mm × 3.0 mm photosensitive segments arranged in an 8 × 8 array. Here, we note that the CTR performance also significantly depends on the timing detection method, which generates a timing trigger signal for coincidence detection. Thus, we evaluated the CTRs for each scintillator structure by adopting four timing detection methods: using the total sum signal of 64 MPPC chips (T_sum), the maximum signal in the 64 MPPC chips (Max), the sum signal of a partial number of MPPC chips located at and in the vicinity of theγ-ray interaction position (P_sum), and the average of the timestamps generated at several MPPC chips (Ave). When using the T_sum for timing detection, the CTR full width at half-maximum values were ∼100 ps regardless of the scintillator structure. However, when using the Max signal approach, the CTRs of the monolithic plates, laser-processing arrays, and fine-pitch laser-processing arrays were drastically degraded with increasing thickness. On the other hand, the CTRs of the pixelated arrays exhibited almost no degradation. To improve the CTRs of the monolithic plate and the (fine-pitch) laser-processing array that exhibit a large light spread in the scintillator block, we applied the P_sum and Ave methods. The resulting CTRs significantly improved upon using P_sum; however, in the Ave approach the improvement effect disappeared when the thickness was <6 mm in case of our simulation.

Performance evaluation of a high-resolution brain PET scanner using four-layer MPPC DOI detectors.

A high-resolution positron emission tomography (PET) scanner, dedicated to brain studies, was developed and its performance was evaluated. A four-layer depth of interaction detector was designed containing five detector units axially lined up per layer board. Each of the detector units consists of a finely segmented (1.2 mm) LYSO scintillator array and an 8 × 8 array of multi-pixel photon counters. Each detector layer has independent front-end and signal processing circuits, and the four detector layers are assembled as a detector module. The new scanner was designed to form a detector ring of 430 mm diameter with 32 detector modules and 168 detector rings with a 1.2 mm pitch. The total crystal number is 655 360. The transaxial and axial field of views (FOVs) are 330 mm in diameter and 201.6 mm, respectively, which are sufficient to measure a whole human brain. The single-event data generated at each detector module were transferred to the data acquisition servers through optical fiber cables. The single-event data from all detector modules were merged and processed to create coincidence event data in on-the-fly software in the data acquisition servers. For image reconstruction, the high-resolution mode (HR-mode) used a 1.2 mm2 crystal segment size and the high-speed mode (HS-mode) used a 4.8 mm2 size by collecting 16 crystal segments of 1.2 mm each to reduce the computational cost. The performance of the brain PET scanner was evaluated. For the intrinsic spatial resolution of the detector module, coincidence response functions of the detector module pair, which faced each other at various angles, were measured by scanning a 0.25 mm diameter 22Na point source. The intrinsic resolutions were obtained with 1.08 mm full width at half-maximum (FWHM) and 1.25 mm FWHM on average at 0 and 22.5 degrees in the first layer pair, respectively. The system spatial resolutions were less than 1.0 mm FWHM throughout the whole FOV, using a list-mode dynamic RAMLA (LM-DRAMA). The system sensitivity was 21.4 cps kBq-1 as measured using an 18F line source aligned with the center of the transaxial FOV. High count rate capability was evaluated using a cylindrical phantom (20 cm diameter × 70 cm length), resulting in 249 kcps in true and 27.9 kcps at 11.9 kBq ml-1 at the peak count in a noise equivalent count rate (NECR_2R). Single-event data acquisition and on-the-fly software coincidence detection performed well, exceeding 25 Mcps and 2.3 Mcps for single and coincidence count rates, respectively. Using phantom studies, we also demonstrated its imaging capabilities by means of a 3D Hoffman brain phantom and an ultra-micro hot-spot phantom. The images obtained were of acceptable quality for high-resolution determination. As clinical and pre-clinical studies, we imaged brains of a human and of small animals.

Novel crystal timing calibration method based on total variation.

A novel crystal timing calibration method based on total variation (TV), abbreviated as 'TV merge', has been developed for a high-resolution positron emission tomography (PET) system. The proposed method was developed for a system with a large number of crystals, it can provide timing calibration at the crystal level. In the proposed method, the timing calibration process was formulated as a linear problem. To robustly optimize the timing resolution, a TV constraint was added to the linear equation. Moreover, to solve the computer memory problem associated with the calculation of the timing calibration factors for systems with a large number of crystals, the merge component was used for obtaining the crystal level timing calibration values. Compared with other conventional methods, the data measured from a standard cylindrical phantom filled with a radioisotope solution was sufficient for performing a high-precision crystal-level timing calibration. In this paper, both simulation and experimental studies were performed to demonstrate the effectiveness and robustness of the TV merge method. We compare the timing resolutions of a 22Na point source, which was located in the field of view (FOV) of the brain PET system, with various calibration techniques. After implementing the TV merge method, the timing resolution improved from 3.34 ns at full width at half maximum (FWHM) to 2.31 ns FWHM.

Development of on-chip fully automated immunoassay system "µTASWako i30" to measure the changes in glycosylation profiles of alpha-fetoprotein in patients with hepatocellular carcinoma.

Glycosylation profiles significantly change during oncogenesis. Aberrant glycosylation can be used as a cancer biomarker in clinical settings. Different glycoforms can be separately detected using lectin affinity electrophoresis and lectin array-based methods. However, most methodologies and procedures need experienced technique to perform the assays and expertise to interpret the results. To apply glycomarkers for clinical practice, a robust assay system with an easy-to-use workflow is required. Wako's µTASWako i30, a fully automated immunoanalyzer, was developed for in vitro diagnostics based on microfluidic technology. It utilizes the principles of liquid-phase binding assay, where immunoreactions are performed in a liquid phase, and electrokinetic analyte transport assay. Capillary electrophoresis on microfluidic chip has enabled the detection of different glycoform types of alpha-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma. AFP with altered glycosylation can be separated based on the reactivity to Lens culinaris agglutinin on electrophoresis. The glycoform AFP-L3 was reportedly more specific in hepatocellular carcinoma. This assay system can provide a high sensitivity and rapid results in 9 min. The test results for ratio of AFP-L3 to total AFP using µTASWako i30 are correlated with those of conventional methodology. The µTASWako assay system and the technology can be utilized for glycosylation analysis in the postgenomic era.

An animal PET scanner using flat-panel position-sensitive PMTs.

OBJECTIVE: To design, build, and evaluate an animal PET scanner, which can be used with non-human primates under conscious condition, incorporating flat-panel position-sensitive photomultiplier tubes (PS-PMTs). METHODS: The system contains 30 detector modules, each having two PS-PMTs and 16×18 lutetium­yttrium oxyortho-silicate scintillation crystal arrays. The system has 17,280 crystals (480 per ring) arranged in 36 rings, with a diameter of 508 mm and axial extent of 108 mm. The gantry tilt mechanism enables PET studies to be performed on a monkey in the sitting position. Data can be acquired in either the 2D or 3D mode, with the slice collimators being retracted in the 3D mode. RESULTS: At the center of the field-of-view, radial resolution is 2.7 mm full width at half maximum (FWHM) and tangential resolution is 2.4 mm FWHM, while axial resolution is 2.5 mm FWHM for direct slices and 2.7 mm FWHM for cross slices. Scatter fraction, count rate capability, and sensitivity were evaluated using a cylindrical phantom 10 cm in diameter. The noise equivalent count rate in the 3D mode is equivalent to that in the 2D mode at a three times higher radioactivity level. Total system sensitivity is 1.3 kcps/(kBq/mL) in 2D mode and 7.4 kcps/(kBq/mL) in the 3D mode. Animal studies with a monkey were performed to evaluate the imaging capabilities of the scanner. CONCLUSION: The new PET scanner will be a useful research tool with non-human primates for pre-clinical drug development.

Alterations in α4ß2 nicotinic receptors in cognitive decline in Alzheimer's aetiopathology.

Nicotinic acetylcholine receptor subtype α4ß2 is considered important in the regulation of attention and memory, and cholinergic degeneration is known as one pathophysiology of Alzheimer's disease. Brain amyloid-ß protein deposition is also a key pathological marker of Alzheimer's disease. Recent amyloid-ß imaging has shown many cognitively normal subjects with amyloid-ß deposits, indicating a missing link between amyloid-ß deposition and cognitive decline. To date, the relationship between the α4ß2 nicotinic acetylcholine receptor and amyloid-ß burden has not been elucidated in vivo. In this study we investigated the relation between α4ß2 nicotinic acetylcholine receptor availability in the brain, cognitive functions and amyloid-ß burden in 20 non-smoking patients with Alzheimer's disease at an early stage and 25 age-matched non-smoking healthy elderly adults by measuring levels of α4ß2 nicotinic acetylcholine receptor binding estimated from a simplified ratio method (BPRI) and Logan plot-based amyloid-ß accumulation (BPND) using positron emission tomography with α4ß2 nicotinic acetylcholine receptor tracer (18)F-2FA-85380 and (11)C-Pittsburgh compound B. The levels of tracer binding were compared with clinical measures for various brain functions (general cognition, episodic and spatial memory, execution, judgement, emotion) using regions of interest and statistical parametric mapping analyses. Between-group statistical parametric mapping analysis showed a significant reduction in (18)F-2FA-85380 BPRI in the cholinergic projection region in patients with Alzheimer's disease with a variety of (11)C-Pittsburgh compound B accumulation. Spearman rank correlation analyses showed positive correlations of (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region with scores of the Frontal Assessment Battery (a test battery for executive functions and judgement) in the Alzheimer's disease group (P < 0.05 corrected for multiple comparison), and also positive correlations of the prefrontal and superior parietal (18)F-2FA-85380 BPRI values with the Frontal Assessment Battery score in the normal group (P < 0.05 corrected for multiple comparison). These positive correlations indicated an in vivo α4ß2 nicotinic acetylcholine receptor role in those specific functions that may be different from memory. Both region of interest-based and voxelwise regression analyses showed a negative correlation between frontal (11)C-Pittsburgh compound B BPND and (18)F-2FA-85380 BPRI values in the medial frontal cortex and nucleus basalis magnocellularis region in patients with Alzheimer's disease (P < 0.05 corrected for multiple comparison). These findings suggest that an impairment of the cholinergic α4ß2 nicotinic acetylcholine receptor system with the greater amount of amyloid deposition in the system plays an important role in the pathophysiology of Alzheimer's disease.

Potential for reducing the numbers of SiPM readout surfaces of laser-processed X'tal cube PET detectors.

We are developing a three-dimensional (3D) position-sensitive detector with isotropic spatial resolution, the X'tal cube. Originally, our design consisted of a crystal block for which all six surfaces were covered with arrays of multi-pixel photon counters (MPPCs). In this paper, we examined the feasibility of reducing the number of surfaces on which a MPPC array must be connected with the aim of reducing the complexity of the system. We evaluated two kinds of laser-processed X'tal cubes of 3 mm and 2 mm pitch segments while varying the numbers of the 4 × 4 MPPC arrays down to two surfaces. The sub-surface laser engraving technique was used to fabricate 3D grids into a monolithic crystal block. The 3D flood histograms were obtained by the Anger-type calculation. Two figures of merit, peak-to-valley ratios and distance-to-width ratios, were used to evaluate crystal identification performance. Clear separation was obtained even in the 2-surface configuration for the 3 mm X'tal cube, and the average peak-to-valley ratios and the distance-to-width ratios were 6.7 and 2.6, respectively. Meanwhile, in the 2 mm X'tal cube, the 6-surface configuration could separate all crystals and even the 2-surface case could also, but the flood histograms were relatively shrunk in the 2-surface case, especially on planes parallel to the sensitive surfaces. However, the minimum peak-to-valley ratio did not fall below 3.9. We concluded that reducing the numbers of MPPC readout surfaces was feasible for both the 3 mm and the 2 mm X'tal cubes.

Intrinsic spatial resolution evaluation of the X'tal cube PET detector based on a 3D crystal block segmented by laser processing.

The X'tal cube is a depth-of-interaction (DOI)-PET detector which is aimed at obtaining isotropic resolution by effective readout of scintillation photons from the six sides of a crystal block. The X'tal cube is composed of the 3D crystal block with isotropic resolution and arrays of multi-pixel photon counters (MPPCs). In this study, to fabricate the 3D crystal block efficiently and precisely, we applied a sub-surface laser engraving (SSLE) technique to a monolithic crystal block instead of gluing segmented small crystals. The SSLE technique provided micro-crack walls which carve a groove into a monolithic scintillator block. Using the fabricated X'tal cube, we evaluated its intrinsic spatial resolution to show a proof of concept of isotropic resolution. The 3D grids of 2 mm pitch were fabricated into an 18 × 18 × 18 mm(3) monolithic lutetium yttrium orthosilicate (LYSO) crystal by the SSLE technique. 4 × 4 MPPCs were optically coupled to each surface of the crystal block. The X'tal cube was uniformly irradiated by (22)Na gamma rays, and all of the 3D grids on the 3D position histogram were separated clearly by an Anger-type calculation from the 96-channel MPPC signals. Response functions of the X'tal cube were measured by scanning with a (22)Na point source. The gamma-ray beam with a 1.0 mm slit was scanned in 0.25 mm steps by positioning of the X'tal cube at vertical and 45° incident angles. The average FWHM resolution at both incident angles was 2.1 mm. Therefore, we confirmed the isotropic spatial resolution performance of the X'tal cube.

A single-ring OpenPET enabling PET imaging during radiotherapy.

We develop an OpenPET system which can provide an accessible open space to the patient during PET scanning. Our first-generation OpenPET geometry which we called dual-ring OpenPET consisted of two separated detector rings and it could extend its axial field of view (FOV) therefore enabling imaging the gap region in addition to the in-ring region. However, applications such as dose verification by in-beam PET measurement during particle therapy and real-time tumor tracking by PET require sensitivity focused onto the gap rather than on the wide FOV. In this paper, we propose a second-generation OpenPET geometry, single-ring OpenPET, which can provide an accessible and observable open space with higher sensitivity and a reduced number of detectors than the earlier one. The proposed geometry has a cylinder shape cut at a slant angle, in which the shape of each cut end becomes an ellipse. We provided a theoretical analysis for sensitivity of the proposed geometry, compared with the dual-ring OpenPET and a geometry where the conventional PET was positioned at a slant angle against the patient bed to form an accessible open space, which we called a slant PET. The central sensitivity depends on the solid angle of these geometries. As a result, we found that the single-ring OpenPET has a sensitivity 1.2 times higher than the dual-ring OpenPET and 1.3 times higher than the slant PET when designed for a 600 mm bed width with 300 mm accessible open space and about 200 detector blocks, each with a front area of 2500 mm². In addition, numerical simulation was carried out to show the imaging property of the proposed geometry realized with the ellipsoidal rings and these results indicate that the depth-of-interaction detector can provide uniform resolution even when the detectors are arranged in an ellipsoidal ring.

A SiPM-based isotropic-3D PET detector X'tal cube with a three-dimensional array of 1 mm(3) crystals.

We are developing a novel, general purpose isotropic-3D PET detector X'tal cube which has high spatial resolution in all three dimensions. The research challenge for this detector is implementing effective detection of scintillation photons by covering six faces of a segmented crystal block with silicon photomultipliers (SiPMs). In this paper, we developed the second prototype of the X'tal cube for a proof-of-concept. We aimed at realizing an ultimate detector with 1.0 mm(3) cubic crystals, in contrast to our previous development using 3.0 mm(3) cubic crystals. The crystal block was composed of a 16 × 16 × 16 array of lutetium gadolinium oxyorthosilicate (LGSO) crystals 0.993 × 0.993 × 0.993 mm(3) in size. The crystals were optically glued together without inserting any reflector inside and 96 multi-pixel photon counters (MPPCs, S10931-50P, i.e. six faces each with a 4 × 4 array of MPPCs), each having a sensitive area of 3.0 × 3.0 mm(2), were optically coupled to the surfaces of the crystal block. Almost all 4096 crystals were identified through Anger-type calculation due to the finely adjusted reflector sheets inserted between the crystal block and light guides. The reflector sheets, which formed a belt of 0.5 mm width, were placed to cover half of the crystals of the second rows from the edges in order to improve identification performance of the crystals near the edges. Energy resolution of 12.7% was obtained at 511 keV with almost uniform light output for all crystal segments thanks to the effective detection of the scintillation photons.

Coexistence of cranial and spinal subdural hematomas: case report.

A 47-year-old man presented with chronic cranial subdural hematomas (SDHs) associated with spinal SDH manifesting as onset of severe lumbago revealed in the follow up for bilateral subdural effusions after trauma. Left chronic cranial SDH was first identified. Two months after evacuation of the left chronic cranial SDH, he complained of severe lumbago. Magnetic resonance imaging detected spinal SDH, prior to the diagnosis and treatment of right chronic cranial SDH. The present case of concomitant occurrence of cranial and spinal SDHs suggests that the possibility of spinal SDH should be investigated with magnetic resonance imaging in patients with chronic cranial SDH.

[Case of an idiopathic dissecting aneurysm of the superficial temporal artery: a case report].

Aneurysms of the superficial temporal artery are usually traumatic in origin an are pseudoaneurysms. We present a rare case of an idiopathic dissecting aneurysm of the superficial temporal artery in a 40-year-old man without history of trauma. The patient had a pulsatile mass in the left temporal region. Angiography showed a fusiform dilatation at the left superficial temporal artery and both the true lumen and the false lumen were recognized. Resection of the aneurysm was performed. Postoperatively, the patients complaints disappeared completely. Histopathological examination of the specimen revealed a dissecting aneurysm. We investigated the histological findings by comparing them to angiographical findings.

A case of brain metastasis from pulmonary giant cell carcinoma.

A 74-year old female was admitted to our hospital due to sudden right hemiparesis. Precontrast brain computed tomography (CT) revealed multiple high-density masses consistent with multiple hemorrhage, and chest CT scan demonstrated a mass in the left lung field without hemorrhage. Follow-up CT showed enlargement of the multiple intracerebral hemorrhages. A diagnosis was made of brain metastasis from a rare pure giant cell carcinoma (GCC) of the lung.

[Evaluation of a new, microfluidic chip-based immunoassay for measurement of AFP-L3].

PURPOSE: AFP-L3 is an isoform of a-fetoprotein which has a fucosylated carbohydrate chain, and the fraction of AFP-L3/total AFP (AFP-L3%) specifically increases in hepatocellular carcinoma (HCC) patients and is widely used for screening and prognosis of HCC. The newly developed microTAS method which combines microchip electrophoresis and lectin affinity electrophoresis can rapidly provide AFP-L3% and total AFP measurements simultaneously at higher sensitivity. Here, we evaluated the system to know its analytical performance and clinical utility. METHOD: Fully automated immunoanalyzer, microTASWako i30 which utilizes Liquid-phase Binding Assay-Electrokinetic Analyte Transport Assay (LBA-EATA method) as the assay principle was employed for the measurement of total AFP and AFP-L3%. We evaluated detection sensitivity, precision, accuracy, and correlation of the method. RESULTS: The detection sensitivity was 0.3 ng/ml for both AFP-L1 and L3. The accuracy of the assay was 91.3-105.0% for total AFP. The precision of the assay was CV 1.9% at 2 ng/ml of total AFP, and CV 1.3% for 10% of AFP-L3% at 20ng/ml of total AFP. The microTAS method showed good correlation with the lectin affinity electrophoresis (AFP-L3 Test Wako) and the LBA methods (LBA Wako AFP-L3 on LiBASys) methods, giving correlation coefficient (r) of 0.988 and 0.988, respectively. The microTAS immunoreaction assay time and the total assay time including chip preparation were 1 and 9 min, respectively. CONCLUSION: Since the microchip assay is rapid and highly sensitive, it should have better clinical utility than the current methods.

[Fully automated immunoassay system utilizing microchip electrophoresis].

Application of microTAS (micro Total Analysis Systems) technologies utilizing chips with microfluidic channels to clinical diagnostic testing has drawn a lot of attention since it is expected to contribute to shortening reaction time, reduction of reagent/sample consumption, reducing instrument size, and other advantages of microchip electrophoresis. We have developed a fully automated immunoassay system by employing isotachophoresis followed by capillary gel electrophoresis for immunoreaction and B/F separation in microfluidic channels on polymer microchips. Laser-Induced Fluorescence (LIF) was used for detection of the sandwich immunocomplex composed of DNA-conjugate antibody, antigen and fluorescent dye-conjugated antibody. An immunoassay for PIVKA II was demonstrated on this new microTAS system utilizing the DNA-conjugated anti PIVKA II antibody and the fluorescent-dye labeled anti-prothrombin antibody. The resulting assay showed good assay performance with high sensitivity (LOD = 5mAU/mL), good reproducibility(CV = 1.0 - 5.7%) and good correlation with the commercially available PIVKA II assay kit (regression curve of y = 1.04x + 11.1, r = 0.991). The assay turn around time (TAT) was about 9 min. The PIVKA II assay will be useful for the diagnosis and prognosis of hepatocellular carcinoma.

The generation of lucigenin chemiluminescence from the reaction of guanidino compounds with phenylglyoxal under alkaline conditions and its application.

It is shown that o-carboxyphenylglyoxal, which is converted from ninhydrin by alkali, produces a chemiluminescent lucigenin reaction under alkaline conditions when with reacted with guanidino compounds. It is also demonstrated that phenylglyoxal, which is a model compound of o-carboxyphenylglyoxal, produces a strong chemiluminescent lucigenin reaction under alkaline conditions when reacted with guanidino compounds. Moreover, ESR spectra showed the presence of 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-spin adducts of superoxide anions in a mixture of phenylglyoxal and guanidino compounds under alkaline conditions. It was confirmed that the superoxide anions were generated by the reaction of phenylglyoxal with guanidino compounds under alkaline conditions, thereby causing lucigenin chemiluminescence. The chemiluminescent reaction of lucigenin in a mixture of phenylglyoxal and the guanidino compounds was applied to HPLC for guanidino compounds. The present chemiluminescence-HPLC system has a 2-fold greater sensitivity than chemiluminescence-HPLC using ninhydrin. Arginine, guanidine and methylguanidine were detected in serum from a hemodialysis patient with chronic renal failure.

Photophobia as the visual manifestation of chiasmal compression by unruptured anterior communicating artery aneurysm. Case report.

A 37-year-old woman presented with photophobia without visual loss associated with chiasmal compression by an unruptured anterior communicating artery (AcomA) aneurysm. She had suffered progressive photophobia for one year. Neuroimaging indicated an AcomA aneurysm attached to the chiasm. Photophobia was resolved following clipping of the aneurysm. AcomA aneurysm should be considered in patients who experience photophobia without visual loss.

Automated immunoassay system for AFP-L3% using on-chip electrokinetic reaction and separation by affinity electrophoresis.

Implementation of the on-chip immunoassay for alpha-fetoprotein (AFP)-L3% was achieved using a fully automated microfluidic instrument platform that will prepare the chip and run the assay with a total assay time of less than 10min. Reagent/sample mixing, concentration, and reaction in microfluidic channels occur by the electrokinetic analyte transport assay (EATA) technique, enabling the integration of all assay steps on-chip. The determination of AFP-L3%, a biomarker for hepatocellular carcinoma, was achieved by the presence of Lens culinaris agglutinin in the separation channel, causing separation of the fucosylated isoform, AFP-L3, from the nonfucosylated AFP-L1 by lectin affinity electrophoresis. Laser-induced-fluorescence (LIF) detection was used to quantitate the labeled immunocomplexes. The limit of detection (LOD) was 0.1ng/ml AFP, and assay precision of less than 2% coefficient of variation (CV) was obtained for quantitation from 24 to 922ng/ml total AFP in spiked serum samples. Assay precision of less than 3% CV was obtained for AFP-L3% measurements from 8.5 to 81%. Furthermore, good correlation of test results for 68 patient serum samples with a commercially available reference method (LiBASys assay for AFP-L3%) was obtained, with r(2)=0.981 and slope=1.03.