Improved diagnosis of the number of stenosed coronary artery vessels by segmentation with scatter and photo-peak window data for attenuation correction in myocardial perfusion SPECT.

BACKGROUND: Attenuation correction using segmentation of scatter and photo-peak window data (SSPAC) enables an evaluation of the attenuation map in a patient-specific manner without additional radiation exposure. We compared the accuracy of SSPAC and non-corrected myocardial perfusion scintigraphy methods for diagnosing the number of stenosed coronary artery vessels. METHODS AND RESULTS: We retrospectively reviewed the data from 183 consecutive patients who underwent 99mTc-tetrofosmin stress/rest SPECT examination and a coronary angiography within 3 months. The MPS images were reconstructed with and without SSPAC attenuation correction. We examined the accuracy of the quantitative interpretation using summed differential score in the detection of coronary artery disease (CAD). The attenuation maps were successfully determined in 179 of 183 patients (98%). In terms of the vessel-based diagnostic ability, sensitivity, specificity, positive predictive and negative predictive values of the SSPAC and non-correction methods for diagnosing CAD in individual coronary territories were 77%*, 89%, 74%*, and 90%* vs 51%, 87%, 62%, and 82%, respectively (*P < .05). In 35 patients with multi-vessel CAD, those values were 78%*, 81%, 93%, and 55%* vs 49%, 81%, 89%, and 34%, respectively (*P < .05; AUC: 0.82 vs 0.62, P < .05). CONCLUSION: SSPAC-corrected SPECT myocardial perfusion images exhibit improved accuracy in the detection of the number of stenosed coronary artery vessels, even in patients with multi-vessel CAD.

Clinical, muscle pathological, and genetic features of Japanese facioscapulohumeral muscular dystrophy 2 (FSHD2) patients with SMCHD1 mutations.

Facioscapulohumeral muscular dystrophy 2 (FSHD2) is a genetic muscular disorder characterized by DNA hypomethylation on the 4q-subtelomeric macrosatellite repeat array, D4Z4. FSHD2 is caused by heterozygous mutations in the gene encoding structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1). Because there has been no study on FSHD2 in Asian populations, it is not known whether this disease mechanism is widely seen. To identify FSHD2 patients with SMCHD1 mutations in the Japanese population, bisulfite pyrosequencing was used to measure DNA methylation on the D4Z4 repeat array, and in patients with DNA hypomethylation, the SMCHD1 gene was sequenced by the Sanger method. Twenty patients with D4Z4 hypomethylation were identified. Of these, 13 patients from 11 unrelated families had ten novel and one reported SMCHD1 mutations: four splice-site, two nonsense, two in-frame deletion, two out-of-frame deletion, and one missense mutations. One of the splice-site mutations was homozygous in the single patient identified with this. In summary, we identified novel SMCHD1 mutations in a Japanese cohort of FSHD2 patients, confirming the presence of this disease in a wider population than previously known.

[Application of N-isopropyl-p-[123I] iodoamphetamine quantification of regional cerebral blood flow using iterative reconstruction methods: selection of the optimal reconstruction method and optimization of the cutoff frequency of the preprocessing filter].

In cerebral blood flow tests using N-Isopropyl-p-[123I] Iodoamphetamine "I-IMP, quantitative results of greater accuracy than possible using the autoradiography (ARG) method can be obtained with attenuation and scatter correction and image reconstruction by filtered back projection (FBP). However, the cutoff frequency of the preprocessing Butterworth filter affects the quantitative value; hence, we sought an optimal cutoff frequency, derived from the correlation between the FBP method and Xenon-enhanced computed tomography (XeCT)/cerebral blood flow (CBF). In this study, we reconstructed images using ordered subsets expectation maximization (OSEM), a method of successive approximation which has recently come into wide use, and also three-dimensional (3D)-OSEM, a method by which the resolution can be corrected with the addition of collimator broad correction, to examine the effects on the regional cerebral blood flow (rCBF) quantitative value of changing the cutoff frequency, and to determine whether successive approximation is applicable to cerebral blood flow quantification. Our results showed that quantification of greater accuracy was obtained with reconstruction employing the 3D-OSEM method and using a cutoff frequency set near 0.75-0.85 cycles/cm, which is higher than the frequency used in image reconstruction by the ordinary FBP method.

Generation of germline-competent rat induced pluripotent stem cells.

BACKGROUND: Recent progress in rat pluripotent stem cell technology has been remarkable. Particularly salient is the demonstration that embryonic stem cells (ESCs) in the rat (rESCs) can contribute to germline transmission, permitting generation of gene-modified rats as is now done using mouse ESCs (mESCs) or mouse induced pluripotent stem cells (iPSCs; miPSCs). However, determinations of whether rat iPSCs (riPSCs) can contribute to germ cells are not published. Here we report the germline competency of riPSCs. METHODOLOGY/PRINCIPAL FINDINGS: We generated riPSCs by transducing three mouse reprogramming factors (Oct3/4, Klf4, and Sox2) into rat somatic cells, followed by culture in the presence of exogenous rat leukemia inhibitory factor (rLIF) and small molecules that specifically inhibit GSK3, MEK, and FGF receptor tyrosine kinases. We found that, like rESCs, our riPSCs can contribute to germline transmission. Furthermore we found, by immunostaining of testis from mouse-rat interspecific chimeras with antibody against mouse vasa homolog, that riPSCs can contribute to embryonic development with chimera formation in mice (rat-mouse interspecific chimeras) and to interspecific germlines. CONCLUSIONS/SIGNIFICANCE: Our data clearly demonstrate that using only three reprogramming factors (Oct3/4, Klf4, and Sox2) rat somatic cells can be reprogrammed into a ground state. Our generated riPSCs exhibited germline transmission in either rat-rat intraspecific or mouse-rat interspecific chimeras.