Tsutomu Zeniya

Vessel Imaging by Interferometric Phase-Contrast X-Ray Technique

Background—Phase-contrast x-ray imaging using an x-ray interferometer has great potential to reveal the structures inside soft tissues, because the sensitivity of this method to hydrogen, carbon, nitrogen, and oxygen is ≈1000 times higher than that of the absorption-contrast x-ray method. Imaging of vessels is very important to understand the vascular distribution of organs and tumors, so the possibility of selective angiography based on phase contrast is examined with a physiological material composed of low-atomic-number elements. Methods and Results—Phase-contrast x-ray imaging was performed with a synchrotron x-ray source. Differences in refractive index, d&dgr;, of physiological saline, lactated Ringer’s solution, 5% glucose, artificial blood such as pyridoxylated hemoglobin–polyoxyethylene conjugate, and perfluorotributylamine were measured. Because the d&dgr; of physiological saline has highest contrast, it was used for the phase-contrast x-ray imaging of vessel, and this was compared with absorption-contrast x-ray images. Vessels >0.03 mm in diameter of excised liver from rats and a rabbit were revealed clearly in phase-contrast x-ray imaging, whereas the vessel could not be revealed at all by the absorption-contrast x-ray image. Absorption-contrast x-ray images with iodine microspheres depicted only portal veins >0.1 mm in diameter with nearly the same x-ray dose as the present phase-contrast x-ray imaging. Conclusions—Phase-contrast x-ray imaging explored clear depiction of the vessels using physiological saline with small doses of x-rays.

Multicenter Evaluation of a Standardized Protocol for Rest and Acetazolamide Cerebral Blood Flow Assessment Using a Quantitative SPECT Reconstruction Program and Split-Dose 123I-Iodoamphetamine

SPECT can provide valuable diagnostic and treatment response information in large-scale multicenter clinical trials. However, SPECT has been limited in providing consistent quantitative functional parametric values across the centers, largely because of a lack of standardized procedures to correct for attenuation and scatter. Recently, a novel software package has been developed to reconstruct quantitative SPECT images and assess cerebral blood flow (CBF) at rest and after acetazolamide challenge from a single SPECT session. This study was aimed at validating this technique at different institutions with a variety of SPECT devices and imaging protocols. Methods: Twelve participating institutions obtained a series of SPECT scans on physical phantoms and clinical patients. The phantom experiments included the assessment of septal penetration for each collimator used and of the accuracy of the reconstructed images. Clinical studies were divided into 3 protocols, including intrainstitutional reproducibility, a comparison with PET, and rest–rest study consistency. The results from 46 successful studies were analyzed. Results: Activity concentration estimation (Bq/mL) in the reconstructed SPECT images of a uniform cylindric phantom showed an interinstitution variation of ±5.1%, with a systematic underestimation of concentration by 12.5%. CBF values were reproducible both at rest and after acetazolamide on the basis of repeated studies in the same patient (mean ± SD difference, −0.4 ± 5.2 mL/min/100 g, n = 44). CBF values were also consistent with those determined using PET (−6.1 ± 5.1 mL/min/100 g, n = 6). Conclusion: This study demonstrates that SPECT can quantitatively provide physiologic functional images of rest and acetazolamide challenge CBF, using a quantitative reconstruction software package.

Absolute quantitation of myocardial blood flow with 201 Tl and dynamic SPECT in canine: optimisation and validation of kinetic modelling

Purpose201Tl has been extensively used for myocardial perfusion and viability assessment. Unlike 99mTc-labelled agents, such as 99mTc-sestamibi and 99mTc-tetrofosmine, the regional concentration of 201Tl varies with time. This study is intended to validate a kinetic modelling approach for in vivo quantitative estimation of regional myocardial blood flow (MBF) and volume of distribution of 201Tl using dynamic SPECT.MethodsDynamic SPECT was carried out on 20 normal canines after the intravenous administration of 201Tl using a commercial SPECT system. Seven animals were studied at rest, nine during adenosine infusion, and four after beta-blocker administration. Quantitative images were reconstructed with a previously validated technique, employing OS-EM with attenuation-correction, and transmission-dependent convolution subtraction scatter correction. Measured regional time-activity curves in myocardial segments were fitted to two- and three-compartment models. Regional MBF was defined as the influx rate constant (K1) with corrections for the partial volume effect, haematocrit and limited first-pass extraction fraction, and was compared with that determined from radio-labelled microspheres experiments.ResultsRegional time-activity curves responded well to pharmacological stress. Quantitative MBF values were higher with adenosine and decreased after beta-blocker compared to a resting condition. MBFs obtained with SPECT (MBFSPECT) correlated well with the MBF values obtained by the radio-labelled microspheres (MBFMS) (MBFSPECT = −0.067 + 1.042 × MBFMS, p < 0.001). The three-compartment model provided better fit than the two-compartment model, but the difference in MBF values between the two methods was small and could be accounted for with a simple linear regression.ConclusionAbsolute quantitation of regional MBF, for a wide physiological flow range, appears to be feasible using 201Tl and dynamic SPECT.

A new reconstruction strategy for image improvement in pinhole SPECT

Pinhole single-photon emission computed tomography (SPECT) is able to provide information on the biodistribution of several radioligands in small laboratory animals, but has limitations associated with non-uniform spatial resolution or axial blurring. We have hypothesised that this blurring is due to incompleteness of the projection data acquired by a single circular pinhole orbit, and have evaluated a new strategy for accurate image reconstruction with better spatial resolution uniformity. A pinhole SPECT system using two circular orbits and a dedicated three-dimensional ordered subsets expectation maximisation (3D-OSEM) reconstruction method were developed. In this system, not the camera but the object rotates, and the two orbits are at 90° and 45° relative to the object’s axis. This system satisfies Tuy’s condition, and is thus able to provide complete data for 3D pinhole SPECT reconstruction within the whole field of view (FOV). To evaluate this system, a series of experiments was carried out using a multiple-disk phantom filled with 99mTc solution. The feasibility of the proposed method for small animal imaging was tested with a mouse bone study using 99mTc-hydroxymethylene diphosphonate. Feldkamp’s filtered back-projection (FBP) method and the 3D-OSEM method were applied to these data sets, and the visual and statistical properties were examined. Axial blurring, which was still visible at the edge of the FOV even after applying the conventional 3D-OSEM instead of FBP for single-orbit data, was not visible after application of 3D-OSEM using two-orbit data. 3D-OSEM using two-orbit data dramatically reduced the resolution non-uniformity and statistical noise, and also demonstrated considerably better image quality in the mouse scan. This system may be of use in quantitative assessment of bio-physiological functions in small animals.

Use of a compact pixellated gamma camera for small animal pinhole SPECT imaging

ObjectivesPinhole SPECT which permitsin vivo high resolution 3D imaging of physiological functions in small animals facilitates objective assessment of pharmaceutical development and regenerative therapy in pre-clinical trials. For handiness and mobility, the miniature size of the SPECT system is useful. We developed a small animal SPECT system based on a compact high-resolution gamma camera fitted to a pinhole collimator and an object-rotating unit. This study was aimed at evaluating the basic performance of the detection system and the feasibility of small animal SPECT imaging.MethodsThe gamma camera consists of a 22 × 22 pixellated scintillator array of 1.8 mm × 1.8 mm × 5 mm NaI(TI) crystals with 0.2-mm gap between the crystals coupled to a 2″ flat panel position-sensitive photomultiplier tube (Hamamatsu H8500) with 64 channels. The active imaging region of the camera was 43.8 mm × 43.8 mm. Data acquisition is controlled by a personal computer (Microsoft Windows) through the camera controller. Projection data over 360° for SPECT images are obtained by synchronizing with the rotating unit. The knife-edge pinhole collimators made of tungsten are attached on the camera and have 0.5-mm and 1.0-mm apertures. The basic performance of the detection system was evaluated with99mTc and201T1 solutions. Energy resolution, system spatial resolution and linearity of count rate were measured. Rat myocardial perfusion SPECT scans were sequentially performed following intravenous injection of201T1C1. Projection data were reconstructed using a previously validated pinhole 3D-OSEM method.ResultsThe energy resolution at 140 keV was 14.8% using a point source. The system spatial resolutions were 2.8-mm FWHM and 2.5-mm FWHM for99mTc and201T1 line sources, respectively, at 30-mm source distance (magnification factor of 1.3) using a 1.0-mm pinhole. The linearity between the activity and count rate was good up to 10 kcps. In a rat study, the left ventricular walls were clearly visible in all scans.ConclusionsWe developed a compact SPECT system using compact gamma camera for small animals and evaluated basic physical performances. The present system may be of use for quantitation of biological functions such as myocardial blood flow in small animals.

Experimental Pig Model of Old Myocardial Infarction with Long Survival Leading to Chronic Left Ventricular Dysfunction and Remodeling as Evaluated by PET

A pig model of reduced left ventricular (LV) function and remodeling or chronic heart failure with long survival after myocardial infarction (MI) has not been established. The aim of this study was to evaluate the pathophysiologic status of a pig model of old MI using a series of PET studies. Methods: Twenty-seven male farm pigs were divided into 2 groups: 7 animals in the control group and 20 animals that underwent a proximal coronary artery (CA) occlusion using an ameroid constrictor after distal CA ligation. A series of PET examinations was performed to assess LV volumes, LV functions, myocardial perfusion response to adenosine, and viability as water-perfusable tissue index. Results: The distal CA ligation inhibited arrhythmia during and after the operation, and a transmural anteroseptal MI, with an infarction area of 27% ± 5% of the whole left ventricle, was generated with a survival rate of 75% at 4 mo. Wall motion evaluated by 18F-FDG PET was diffusely reduced, including the noninfarcted wall. Global LV ejection fraction as assessed by gated C15O PET was reduced (39% ± 16%) in the group undergoing occlusion, compared with the control group (66% ± 16%, P < 0.05). LV end-systolic (31.4 ± 9.2 cm3) and end-diastolic (52.7 ± 10.2 cm3) volumes were increased, compared with controls (15.2 ± 9.4 cm3, P < 0.01, and 41.7 ± 11.5 cm3, P < 0.05, respectively). Histology showed hypertrophy and development of microscopic fibrosis in noninfarcted myocardium. PET demonstrated the reduced myocardial perfusion response to adenosine and also reduced water-perfusable tissue index in remote segments. Conclusion: The pig model of old MI generated by the chronic proximal CA obstruction after distal ligation was characterized by LV dysfunction and remodeling, with a high survival rate.

Validity of using a 3-dimensional PET scanner during inhalation of 15O-labeled oxygen for quantitative assessment of regional metabolic rate of oxygen in man

Use of 15O labeled oxygen (15O2) and positron emission tomography (PET) allows quantitative assessment of the regional metabolic rate of oxygen (CMRO2) in vivo, which is essential to understanding the pathological status of patients with cerebral vascular and neurological disorders. The method has, however, been challenging, when a 3D PET scanner is employed, largely attributed to the presence of gaseous radioactivity in the trachea and the inhalation system, which results in a large amount of scatter and random events in the PET assessment. The present study was intended to evaluate the adequacy of using a recently available commercial 3D PET scanner in the assessment of regional cerebral radioactivity distribution during an inhalation of 15O2. Systematic experiments were carried out on a brain phantom. Experiments were also performed on a healthy volunteer following a recently developed protocol for simultaneous assessment of CMRO2 and cerebral blood flow, which involves sequential administration of 15O2 and C15O2. A particular intention was to evaluate the adequacy of the scatter-correction procedures. The phantom experiment demonstrated that errors were within 3% at the practically maximum radioactivity in the face mask, with the greatest radioactivity in the lung. The volunteer experiment demonstrated that the counting rate was at peak during the 15O gas inhalation period, within a verified range. Tomographic images represented good quality over the entire FOV, including the lower part of the cerebral structures and the carotid artery regions. The scatter-correction procedures appeared to be important, particularly in the process to compensate for the scatter originating outside the FOV. Reconstructed images dramatically changed if the correction was carried out using inappropriate procedures. This study demonstrated that accurate reconstruction could be obtained when the scatter compensation was appropriately carried out. This study also suggested the feasibility of using a state-of-the-art 3D PET scanner in the quantitative PET imaging during inhalation of 15O labeled oxygen.

Interferometric X-Ray Imaging of Breast Cancer Specimens at 51 keV X-Ray Energy

The feasibility of the interferometric X-ray imaging technique is examined for revealing the features of breast cancer specimens. The interferometric X-ray imaging system consisted of an asymmetrically cut silicon crystal, a monolithic X-ray interferometer, a phase-shifter, an object cell, and an X-ray CCD camera. Ten 10-mm-thick formalin-fixed breast cancer specimens were imaged at 51 keV, and these images were compared with absorption-contrast X-ray images obtained at 18 keV monochromatic synchrotron X-ray. The interferometric X-ray images clearly depicted the essential features of the breast cancer such as microcalcification down to a size of 0.036 mm, spiculation, and detailed inner soft tissue structures closely matched with histopathological morphology, while the absorption-contrast X-ray images obtained using nearly the same X-ray dose only resolved microcalcification down to a size of 0.108 mm and spiculation. The interferometric X-ray imaging technique can be considered to be an innovative technique for the early and accurate diagnosis of breast cancer using an extremely low X-ray dose.

System design and development of a pinhole SPECT system for quantitative functional imaging of small animals

Recently, small animal imaging by pinhole SPECT has been widely investigated by several researchers. We developed a pinhole SPECT system specially designed for small animal imaging. The system consists of a rotation unit for a small animal and a SPECT camera attached with a pinhole collimator. In order to acquire complete data of the projections, the system has two orbits with angles of 90° and 45° with respect to the object. In this system, the position of the SPECT camera is kept fixed, and the animal is rotated in order to avoid misalignment of the center of rotation (COR). We implemented a three dimensional OSEM algorithm for the reconstruction of data acquired by the system from both the orbitals. A point source experiment revealed no significant COR misalignment using the proposed system. Experiments with a line phantom clearly indicated that our system succeeded in minimizing the misalignment of the COR. We performed a study with a rat and99mTc-HMDP, an agent for bone scan, and demonstrated a dramatic improvement in the spatial resolution and uniformity achieved by our system in comparison with the conventional Feldkamp algorithm with one set of orbital data.

Breath-hold CT attenuation correction for quantitative cardiac SPECT

BackgroundAttenuation correction of a single photon emission computed tomography (SPECT) image is possible using computed tomography (CT)-based attenuation maps with hybrid SPECT/CT. CT attenuation maps acquired during breath holding can be misaligned with SPECT, generating artifacts in the reconstructed images. The purpose of this study was to investigate the effects of respiratory phase during breath-hold CT acquisition on attenuation correction of cardiac SPECT imaging.MethodsA series of 201Tl-emission and 99mTc-based transmission computed tomography (TCT) scans was carried out along with CT-attenuation scans on 11 young normal volunteers using a hybrid SPECT/CT scanner. The CT scans were performed at three respiratory phases: end-inspiration (INS), end-expiration (EXP), and the midpoint (MID) between these phases. Using alignment parameters between attenuation maps and SPECT images without attenuation or scatter corrections, quantitative SPECT images were reconstructed, including corrections for attenuation and scatter. Regional radioactivity concentrations normalized by the subjects’ weights were compared between CT- and TCT-based attenuation correction techniques.ResultsSPECT images with CT attenuation maps at the EXP phase showed significant differences in regional weight-normalized radioactivity concentrations relative to the images using the other attenuation maps (p < 0.05), as well as systematic positive bias errors, compared to TCT-based images for all myocardial segments, 5.7% ± 2.7% (1.9% to 10.0%). No significant differences in regional weight-normalized radioactivity concentrations were observed between images with CT attenuation maps at MID and INS phases or between these and the TCT-based images, but regional tendencies were found: for anterior to anterolateral segment, positive bias of 5.0% ± 2.2% (1.3% to 8.1%) and 5.6% ± 1.9% (2.6% to 8.5%) and for inferior to inferoseptal segment, negative bias of −5.3% ± 2.6% (−9.1% to −1.7%) and −4.6% ± 2.5% (−8.8% to −1.5%) for the MID and INS phases, respectively.ConclusionsUse of breath-hold CT attenuation maps at INS and MID phases for attenuation and scatter corrections demonstrated accurate quantitative images that would prove beneficial in cardiac SPECT/CT studies.