Yuki Hori

Noninvasive detection of pulmonary tissue destruction in a mouse model of emphysema using hyperpolarized 129Xe MRS under spontaneous respiration.

In the present study, a chemical shift saturation recovery method in hyperpolarized 129Xe MR spectroscopy measurements was applied to two groups of spontaneously breathing mice, an elastase‐induced emphysema model and a control group. Parameters detected were those related to lung structures and functions, such as alveolar septal thickness, h, the ratio of the alveolar septal volume relative to gas space volume, Vs/Va, and the transit time of blood through the gas exchange region, τ. To investigate the potential of these parameters as biomarkers, an attempt was made to detect physiologic changes in the lungs of elastase‐treated mice. Our results showed that Vs/Va was significantly reduced in elastase‐treated mice, reflecting emphysema‐like destruction of the alveolar wall. Compared with histologic results, this degree of reduction was shown to reflect the severity of wall destruction. On the other hand, significant changes in other parameters, h and τ, were not shown. This study is the first application of hyperpolarized 129Xe MR spectroscopy to a mouse model of emphysema and shows that the Vs/Va volume ratio is an effective biomarker for emphysema that could become useful in drug research and development through noninvasive detection of pathologic changes in small rodents. Magn Reson Med, 2010.

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.

Hyperpolarized 129Xe lung MRI in spontaneously breathing mice with respiratory gated fast imaging and its application to pulmonary functional imaging

In the present study, a balanced steady‐state free precession pulse sequence combined with compressed sensing was applied to hyperpolarized 129Xe lung imaging in spontaneously breathing mice. With the aid of fast imaging techniques, the temporal resolution was markedly improved in the resulting images. Using these protocols and respiratory gating, 129Xe lung images in end‐inspiratory and end‐expiratory phases were obtained successfully. The application of these techniques for pulmonary functional imaging made it possible to simultaneously evaluate regional ventilation and gas exchange in the same animal. A comparative study between healthy and elastase‐induced mouse models of emphysema showed abnormal ventilation as well as gas exchange in elastase‐treated mice. Copyright

Direct imaging of hyperpolarized 129Xe alveolar gas uptake in a mouse model of emphysema.

MRI of hyperpolarized 129Xe dissolved in pulmonary tissues, and blood has the potential to offer a new tool for regional evaluation of pulmonary gas exchange and perfusion; however, the extremely short T  2* and low magnetization density make it difficult to acquire the image. In this study, an ultrashort echo‐time sequence was introduced, and its feasibility to quantitatively assess emphysema‐like pulmonary tissue destruction by a combination of dissolved‐ and gas‐phase 129Xe lung MRI was investigated. The ultrashort echo‐time has made it possible to acquire dissolved 129Xe images with reasonably high spatial resolution of 0.625 × 0.625 mm2 and to obtain T  2* of 0.67 ± 0.30 ms in a spontaneously breathing mouse at 9.4 T. The regional dynamic alveolar gas uptake as well as subsequent transport by pulmonary blood flow was also visualized. The ratio of 129Xe magnetization that diffused into the septa relative to the gas‐phase magnetization F was regionally evaluated. The mean F value of elastase‐treated mice was 2.28 ± 0.46%, which was significantly reduced from that of control mice 3.41 ± 0.48% (P = 0.0052). This reflects the reduced uptake efficiency due to alveolar tissue destruction and is correlated with the histologically derived alveolar surface‐to‐volume ratio. Magn Reson Med, 2013.

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.

Noninvasive quantification of cerebral metabolic rate for glucose in rats using 18F-FDG PET and standard input function

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed 18F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individuals BM and ID (estimated individual input function, EIFNS) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF1S). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIFNS-, and EIF1S-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIFNS was highly correlated with those derived from AIF and EIF1S. Preliminary comparison between AIF and EIFNS in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIFNS method might serve as a noninvasive substitute for individual AIF measurement.

Adequacy of a Compartment Model for CMRO2 Quantitation Using 15O-Labeled Oxygen and PET: A Clearance Measurement of 15O-Radioactivity Following Intracarotid Bolus Injection of 15O-Labeled Oxyhemoglobin on Macaca Fascicularis

We aimed at evaluating the adequacy of the commonly employed compartmental model for quantitation of cerebral metabolic rate of oxygen (CMRO2) using 15O-labeled oxygen (15O2) and positron emission tomography (PET). Sequential PET imaging was carried out on monkeys following slow bolus injection of blood samples containing 15O2–oxyhemoglobin (15O2–Hb), 15O-labeled water (H215O), and C15O-labeled hemoglobin (C15O–Hb) into the internal carotid artery (ICA). Clearance slopes were assessed in the middle cerebral artery territory of the injected hemisphere. The time–activity curves were bi-exponential for both 15O2–Hb and H215O. Single exponential fitting to the early (5 to 40 seconds) and late (80 to 240 seconds) periods after the peak was performed and the 15O2–Hb and H215O results were compared. It was found that a significant difference between the clearance rates of the 15O2–Hb and H215O injections is unlikely, which supports the mathematical model that is widely used to describe the kinetics of 15O2–Hb and H215O in cerebral tissues and is the basis of recent approaches to simultaneously assess CMRO2 and cerebral blood flow in a single PET session. However, it should be noted that more data are necessary to unequivocally confirm the result.

Ventral striatum links motivational and motor networks during operant-conditioned movement in rats

&NA; Voluntary actions require motives. It is already known that the medial prefrontal cortex (MPFC) assess the motivational values. However, it remains unclear how the motivational process gains access to the motor execution system in the brain. Here we present evidence that the ventral striatum (VS) plays a hub‐like role in mediating motivational and motor processing in operant behavior. We used positron emission tomography (PET) to detect the neural activation areas associated with motivational action. Using obtained regions, partial correlation analysis was performed to examine how the motivational signals propagate to the motor system. The results revealed that VS activity propagated to both MPFC and primary motor cortex through the thalamus. Moreover, muscimol injection into the VS suppressed the motivational behavior, supporting the idea of representations of motivational signals in VS that trigger motivational behavior. These results suggest that the VS‐thalamic pathway plays a pivotal role for both motivational processing through interactions with the MPFC and for motor processing through interactions with the motor BG circuits. HighlightsWe established a procedure for measuring cerebral metabolic changes in rats at the whole brain during forelimb movement.Striatal activities propagate to the medial prefrontal cortex and motor systems in parallel through the thalamus during operant action.Reward‐related and motor‐related circuits have interacted each other through the ventral striatum‐thalamic pathway.

Development of high-resolution brain SPECT system using full-digital gamma camera with multiple position-sensitive PMTs

We are developing brain SPECT system with excellent spatial resolution less than 5 mm like PET system. In this study we developed a full-digital gamma camera with position-sensitive photomultiplier tube (PMT) to achieve high spatial resolution and constructed SPECT system using it. In addition, we evaluated the performance of the developed gamma camera and SPECT system.

Conceptual design of high spatial-resolution SPECT system for human brain

We have designed the concept of practical high spatial-resolution SPECT for human brain. This study suggested combination PSPMTs with full-digital circuit can achieve detector intrinsic spatial resolution less than 2 mm. Image reconstruction software will compensate decrease of sensitivity due to collimator for high resolution. This system is expected to have the system resolution of 3–4 mm and the sensitivity higher than that in conventional clinical SPECT system.