Transthyretin amyloid cardiomyopathy disease burden quantified using 99mTc-pyrophosphate SPECT/CT: volumetric parameters versus SUVmax ratio at 1 and 3 hours.

BACKGROUND: Various parameters derived from technetium-99m pyrophosphate (99mTc-PYP) single-photon emission computed tomography (SPECT) correlate with the severity of transthyretin amyloid cardiomyopathy (ATTR-CM). However, the optimal metrics and image acquisition timing required to quantify the disease burden remain uncertain. METHODS AND RESULTS: We retrospectively evaluated 99mTc-PYP SPECT/CT images of 23 patients diagnosed with ATTR-CM using endomyocardial biopsies and/or gene tests. All patients were assessed by SPECT/CT 1 hour after 99mTc-PYP injection, and 13 of them were also assessed at 3 hours. We quantified 99mTc-PYP uptake using the volumetric parameters, cardiac PYP volume (CPV) and cardiac PYP activity (CPA). We also calculated the SUVmax ratios of myocardial SUVmax/blood pool SUVmax, myocardial SUVmax/bone SUVmax, and the SUVmax retention index. We assessed the correlations between uptake parameters and the four functional parameters associated with prognosis, namely left ventricular ejection fraction, global longitudinal strain, myocardial extracellular volume, and troponin T. CPV and CPA correlated more closely than the SUVmax ratios with the four prognostic factors. Significant correlations between volumetric parameters and prognostic factors were equivalent between 1 and 3 hours. CONCLUSIONS: The disease burden of ATTR-CM was quantified more accurately by volumetric evaluation of 99mTc-PYP SPECT/CT than SUVmax ratios and the performance was equivalent between 1 and 3 hours.

Volumetric evaluation of 99mTc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters.

BACKGROUND: Volumetric evaluation of 99mTechnetium-pyrophosphate (99mTc-PYP) SPECT/CT is a useful method for assessing transthyretin cardiac amyloidosis (ATTR-CA). We investigated the methodology and assessed its relationship with conventional parameters. METHODS AND RESULTS: We retrospectively evaluated 99mTc-PYP SPECT/CT scans of 25 patients who underwent endomyocardial biopsy and/or gene testing. Fourteen (56%) patients were diagnosed with ATTR-CA. SPECT/CT images were acquired at 3 hours after injection. Total volumes of the myocardial regions where uptakes were > 1.2 and 1.4 × aortic blood pool SUVmax were evaluated and defined as cardiac pyrophosphate volume (CPV1.2 and CPV1.4). The heart-to-contralateral lung (H/CL) ratio and myocardial SUVmax were also calculated. CPV1.2 achieved the highest sensitivity and specificity in diagnosing ATTR-CA. In patients diagnosed with ATTR-CA (n = 14), CPV1.2 negatively correlated with left ventricular ejection fraction and positively correlated with left ventricular posterior wall thickness and QRS duration. The correlation was stronger in CPV1.2 than in the H/CL ratio and SUVmax. CONCLUSION: Volumetric evaluation of 99mTc-PYP SPECT/CT may be superior to the H/CL ratio and SUVmax in assessing the disease burden of ATTR-CA. Larger studies are warranted to clarify whether volumetric measurement can assess prognosis and disease progression.

The utility of heart-to-mediastinum ratio using a planar image created from IQ-SPECT with Iodine-123 meta-iodobenzylguanidine.

AIMS: 123I-labeled meta-iodobenzylguanidine (MIBG) has used a planar image to measure the heart-to-mediastinum ratio (HMR). However, planar images are not available from IQ-SPECT with SMARTZOOM collimator due to its multi-focal collimation. Since we created the planar-equivalent (IQ-planar) images by adding all slices of the IQ-SPECT coronal image. The aim of this study was to demonstrate the utility of the new method for calculating HMR. METHODS: The planar image and transverse images of IQ-SPECT with attenuation and scatter corrections (ACSC) and without ACSC (NC) were obtained. Multi-planar reconstruction and ray-summation processing were applied to create IQ-planar images with NC and ACSC. Linear regression between the measured HMR from the planar image and the mathematically calculated HMR was used to calibrate HMR to standardized values. RESULTS: Scatterplots and linear regression lines between planar and IQ-planar HMRs before and after cross-calibration showed systematic differences in both NC and ACSC conditions. The IQ-planar HMR with NC and ACSC was significantly higher compared with that of the conventional planar image. However, the IQ-planar HMR with NC and ACSC after cross-calibration was similar to the standardized HMR calculated by planar image. CONCLUSION: The IQ-planar HMR using the new ray-summation processing method could be used along with the conventional planar HMR.

Hybrid surgical and endovascular repair for anastomotic pseudoaneurysms after total arch replacement.

An 83-year-old woman who had undergone total arch replacement for a thoracic aortic aneurysm seven years prior experienced concurrent rupture of second and third branch anastomotic pseudoaneurysms. A stent graft was initially deployed across the pseudoaneurysm from the third branch to the left subclavian artery. Following the left axillary and left carotid arterial bypass, the origin of the second branch was embolized with metallic coils. As a result, both anastomotic pseudoaneurysms were undetectable by both completion angiogram and postoperative CT. By combining surgical and endovascular procedures, ruptured anastomotic pseudoaneurysms after total arch replacement can be repaired without a risky resternotomy.

[Surgical Treatment for Congenital Bronchial Atresia and Intralobar Sequestration in the Same Lobe].

A 21-year-old man who had a history of pneumonia twice presented with chest discomfort. Computed tomography( CT) revealed dilatation of the atretic bronchus that was not continuous with the proximal one, and surrounding hyper-lucent lung fields in the outer and mediastinal sides of the right basal segment, and the absence of B10b+c. CT also demonstrated the presence of A10b+c in the former field and the aberrant artery from the inferior phrenic artery in the latter. Right basal segmentectomy was performed under the diagnosis of congenital bronchial atresia and intralobar sequestration. Pathological diagnosis accorded with preoperative one.

Asymmetric Synthesis of a 5,6,7,8-Tetrahydro-1,6-naphthyridine Scaffold Leading to Potent Retinoid-Related Orphan Receptor γt Inverse Agonist TAK-828F.

An asymmetric synthesis of the tetrahydronaphthyridine scaffold of TAK-828F as a RORγt inverse agonist has been developed. The synthesis features a newly discovered atom-economical protocol for Heck-type vinylation of chloropyridine using ethylene gas, an unprecedented formation of dihydronaphthyridine directly from 2-vinyl-3-acylpyridine mediated by ammonia, and a ruthenium-catalyzed enantioselective transfer hydrogenation as key steps. This represents the first example of the enantioselective synthesis of a 5,6,7,8-tetrahydro-1,6-naphthyridine compound. The new synthesis is also free of chromatography or distillation purification processes and therefore qualifies for extension to large-scale manufacture.

Detection of the artery of Adamkiewicz using multidetector row computed tomography in patients with spinal arteriovenous shunt disease.

PURPOSE: To plan a treatment strategy for a spinal arteriovenous shunt (SAVS), identifying the artery of Adamkiewicz (AKA) and its origin is indispensable. However, detecting the AKA is very difficult in patients with an SAVS when using computed tomography angiography (CTA) by the usual method to find the hairpin curved artery because dilated drainage veins nearly always coexist with the hairpin curved AKA. We designed a method to identify the AKA by focusing on the diameter and pathway of the anterior radiculomedullary arteries (RMAs). MATERIAL AND METHODS: Seven consecutive patients with an SAVS were surveyed. They underwent contrast-enhanced CTA and conventional angiography from January 2009 to December 2012. Two readers evaluated the CTA images and assumed that the AKA was the artery that ran through the anterior portion of the neural foramen and continued to pass on the ventral side of the spinal cord. RESULTS: Among the seven patients, nine AKAs were detected with conventional angiography. When using our method, seven AKAs and six AKAs were identified on CTA by Reader 1 and Reader 2, respectively. The average sensitivity was 72.3%, and the specificity, accuracy, positive predictive value, and negative predictive value were sufficiently high (i.e. > 85%) for both readers. The kappa value for detecting the AKA was 0.98. CONCLUSIONS: Detecting the origin of the AKA with CTA is challenging in patients with an SAVS. However, focusing on the diameter and pathway of the RMAs may allow successful identification.

[Influence of the Each Correction Method for the Specific Binding Ratio and Standardized Uptake Value in the Dopamine Transporter SPECT].

This study was to reveal the characteristics for each correction effect of specific binding ratio (SBR) and standardized uptake value (SUV) in the dopamine transporter (DAT) single photon emission computed tomography (SPECT). We created the 123I solution of five radioactive concentrations, which was filled with two types of striatum phantom such as separated or integrated caudate and putamen. We created 10 striatum accumulation models by combining the 123I solution. Images were reconstructed using ordered subset expectation maximization (OSEM) incorporating attenuation correction (AC), scatter correction (SC) or resolution recovery (RR) for the collected data of 10 striatum accumulation models and 66 patients. Correction combinations were AC, ACSC, ACRR and ACSCRR. The SBR, SUVmean and SUVmax were evaluated correlation and relative error between SBR, SUVmean and SUVmax by each correction method. The SBR and SUV had a significant positive correlation with all correction methods. The minimum values of relative error for SBR, SUVmean and SUVmax were 39.7% with ACSCRR, 18.4% with AC and 16.5% with ACSC, respectively. In addition, the ACSC of SBR and SUVmean was almost same value. The SBR showed significantly higher values by incorporating SC, while the SUV was significantly higher values by incorporating RR. It was suggested that SUV could be used for the quantitative index of DAT SPECT. Furthermore, we demonstrated the characteristic among each correction for SBR and SUV.

Creation and characterization of normal myocardial perfusion imaging databases using the IQ·SPECT system.

BACKGROUND: Image acquisition by short-time single-photon emission-computed tomography (SPECT) has been made feasible by IQ·SPECT. The aim of this study was to generate normal databases (NDBs) of thallium-201 (201Tl) myocardial perfusion imaging for IQ·SPECT, and characterize myocardial perfusion distribution. METHODS AND RESULTS: We retrospectively enrolled 159 patients with a low likelihood of cardiac diseases from four hospitals in Japan. All patients underwent short-time 201Tl myocardial perfusion IQ·SPECT with or without attenuation and scatter correction (ACSC) in either supine or prone position. The mean myocardial counts were calculated using 17-segment polar maps. Three NDBs were derived from supine and prone images as well as supine images with ACSC. Differences between the supine and prone positions were observed in the uncorrected sex-segregated NDBs in the mid-inferolateral counts (p ≤ 0.016 for males and p ≤ 0.002 for females). Differences between IQ·SPECT and conventional SPECT were also observed in the mid-anterior, inferolateral, and apical lateral counts (p ≤ 0.009 for males and p ≤ 0.003 for females). Apical low counts attributed to myocardial thinning were observed in the apical anterior and apex segments in the supine IQ·SPECT NDB with ACSC. CONCLUSIONS: There were significant differences between uncorrected supine and prone NDBs, between uncorrected supine NDB and supine NDB with ACSC, and between uncorrected supine NDB and conventional SPECT NDB. Understanding the pattern of normal distribution in IQ-SPECT short-time acquisitions with and without ACSC will be helpful for interpretation of imaging findings in patients with coronary artery disease (CAD) or low likelihood of CAD and the NDBs will aid in quantitative analysis.

Endoleak detection after endovascular aneurysm repair using unenhanced MRI with flow suppression technique: Feasibility study in comparison with contrast-enhanced CT.

OBJECTIVES: To evaluate the feasibility of unenhanced motion-sensitized-driven equilibrium (MSDE)-prepared balanced turbo field echo (BTFE) sequences for detecting endoleaks after endovascular aneurysm repair (EVAR). METHODS: Forty-six patients treated with EVAR for aortic and/or iliac arterial aneurysms underwent contrast-enhanced CT and MSDE-prepared BTFE sequences with and without flow suppression. Two independent observers reviewed these sequences and their subtraction images and assigned confidence levels for detecting endoleaks. Relative contrast values were calculated by dividing signal intensities by those of paraspinal muscles. CT provided the reference standard. RESULTS: CT showed types I and II endoleaks in one and ten patients, respectively. Areas under receiver operating characteristic curves were 0.92 and 0.97 for observers 1 and 2, respectively. Sensitivity, specificity, accuracy, positive predictive value and negative predictive value of both observers were 91 (10/11), 91(32/35), 91 (42/46), 77 (10/13) and 97 % (32/33), respectively. Relative contrast values of endoleaks and flowing blood significantly decreased by flow suppression on MSDE-prepared BTFE images (P = 0.002 and P < 0.0001 respectively), and were significantly higher than those of the excluded aneurysms on subtraction images (P = 0.003 and P = 0.001, respectively). CONCLUSIONS: Unenhanced MSDE-prepared BTFE sequences are feasible for detecting endoleaks. KEY POINTS: • Flow suppression significantly reduces endoleak signals on MSDE-prepared BTFE images. • Subtraction images of MSDE-prepared BTFE sequences ± flow suppression demonstrate endoleaks. • MSDE-prepared BTFE sequences indicate high diagnostic values (>90 %) except PPV (77 %). • MSDE-prepared BTFE sequences need further refinement to reduce false positives. • Endoleaks can be detected without contrast injection using MSDE-prepared BTFE sequences.

Genome-wide genetic screen identified the link between dG9a and epidermal growth factor receptor signaling pathway in vivo.

G9a is one of the histone H3 Lys 9 (H3K9) specific methyltransferases first identified in mammals. Drosophila G9a (dG9a) has been reported to induce H3K9 dimethylation in vivo, and the target genes of dG9a were identified during embryonic and larval stages. Although dG9a is important for a variety of developmental processes, the link between dG9a and signaling pathways are not addressed yet. Here, by genome-wide genetic screen, taking advantage of the rough eye phenotype of flies that over-express dG9a in eye discs, we identified 16 genes that enhanced the rough eye phenotype induced by dG9a over-expression. These 16 genes included Star, anterior open, bereft and F-box and leucine-rich repeat protein 6 which are components of epidermal growth factor receptor (EGFR) signaling pathway. When dG9a over-expression was combined with mutation of Star, differentiation of R7 photoreceptors in eye imaginal discs as well as cone cells and pigment cells in pupal retinae was severely inhibited. Furthermore, the dG9a over-expression reduced the activated ERK signals in eye discs. These data demonstrate a strong genetic link between dG9a and the EGFR signaling pathway.

Genomewide identification of target genes of histone methyltransferase dG9a during Drosophila embryogenesis.

Post-translational modification of the histone plays important roles in epigenetic regulation of various biological processes. Among the identified histone methyltransferases (HMTases), G9a is a histone H3 Lys 9 (H3K9)-specific example active in euchromatic regions. Drosophila G9a (dG9a) has been reported to feature H3K9 dimethylation activity in vivo. Here, we show that the time required for hatching of a homozygous dG9a null mutant and heteroallelic combination of dG9a null mutants is delayed, suggesting that dG9a is at least partially responsible for progression of embryogenesis. Immunocytochemical analyses of the wild-type and the dG9a null mutant flies indicated that dG9a localizes in cytoplasm up to nuclear division cycle 7 where it is likely responsible for di-methylation of nucleosome-free H3K9. From cycles 8-11, dG9a moves into the nucleus and is responsible for di-methylating H3K9 in nucleosomes. RNA-sequence analysis utilizing early wild-type and dG9a mutant embryos showed that dG9a down-regulates expression of genes responsible for embryogenesis. RNA fluorescent in situ hybridization analysis further showed temporal and spatial expression patterns of these mRNAs did not significantly change in the dG9a mutant. These results indicate that dG9a controls transcription levels of some zygotic genes without changing temporal and spatial expression patterns of the transcripts of these genes.

Organ Atrophy Induced by Sorafenib and Sunitinib - Quantitative Computed Tomography (CT) Evaluation of the Pancreas, Thyroid Gland and Spleen.

BACKGROUND: To evaluate organ atrophy induced by sorafenib and sunitinib, we retrospectively reviewed the CT scans of renal cell carcinoma (RCC) patients receiving molecular targeted therapy (MTT) using sorafenib or sunitinib, and performed volumetric analysis of the pancreas, thyroid gland, and spleen. MATERIAL/METHODS: Thirteen RCC patients receiving MTT were assigned as the evaluation cases (MTT group), while thirteen additional RCC patients not receiving MTT were retrieved as the Control group. We evaluated the baseline and follow-up CT studies. The volume of the three organs estimated by CT volumetry was compared between the baseline and follow-up CTs. The atrophic ratio of the organ volume in the follow-up CT to that in the baseline CT was calculated, and compared between the MTT and Control groups. RESULTS: All measured organs in the MTT group showed statistically significant volume loss, while no significant change was observed in the Control group. Mean atrophic ratio in the MTT group was 0.74, 0.58, and 0.82 for the pancreas, thyroid and spleen, respectively. The differences in atrophic ratios between both groups were all statistically significant (P<0.05). CONCLUSIONS: Single-agent sorafenib or sunitinib therapy induced statistically significant atrophy in the pancreas, thyroid, and spleen.

Congenital focal lymphedema as a diagnostic clue to tuberous sclerosis complex: report of two cases diagnosed by ultrasound.

Tuberous sclerosis complex (TSC) is a familial disorder characterized by benign hamartomas in the brain and other organs. Generally, the diagnosis of TSC is relatively easy, based on a medical history, a physical examination, and imaging findings. However, it can be difficult to consider a possibility of TSC in neonates and infants when congenital lymphedema is the sole external manifestation, because lymphedema associated with TSC is extremely rare. Herein, we report two cases of TSC showing congenital lymphedema at the initial presentation. Both patients were girls, and their sole complaint was congenital lymphedema. We diagnosed TSC using ultrasound focusing on the kidney, heart, and brain in addition to the extremity showing lymphedema. Awareness of a potential association of congenital lymphedema with TSC may assist in the diagnosis of TSC by ultrasound.

[The Optimal Reconstruction Parameters by Scatter and Attenuation Corrections Using Multi-focus Collimator System in Thallium-201 Myocardial Perfusion SPECT Study].

The aim of this study was to reveal the optimal reconstruction parameters of ordered subset conjugates gradient minimizer (OSCGM) by no correction (NC), attenuation correction (AC), and AC+scatter correction (ACSC) using IQ-single photon emission computed tomography (SPECT) system in thallium-201 myocardial perfusion SPECT. Myocardial phantom acquired two patterns, with or without defect. Myocardial images were performed 5-point scale visual score and quantitative evaluations using contrast, uptake, and uniformity about the subset and update (subset×iteration) of OSCGM and the full width at half maximum (FWHM) of Gaussian filter by three corrections. We decided on optimal reconstruction parameters of OSCGM by three corrections. The number of subsets to create suitable images were 3 or 5 for NC and AC, 2 or 3 for ACSC. The updates to create suitable images were 30 or 40 for NC, 40 or 60 for AC, and 30 for ACSC. Furthermore, the FWHM of Gaussian filters were 9.6 mm or 12 mm for NC and ACSC, 7.2 mm or 9.6 mm for AC. In conclusion, the following optimal reconstruction parameters of OSCGM were decided; NC: subset 5, iteration 8 and FWHM 9.6 mm, AC: subset 5, iteration 8 and FWHM 7.2 mm, ACSC: subset 3, iteration 10 and FWHM 9.6 mm.

Detectability of cold tumors by xSPECT bone technology compared with hot tumors: a supine phantom study.

Detecting cold as well as hot tumors is vital for interpreting bone tumors on single-photon emission computed tomography (SPECT) images. This study aimed to visually and quantitatively demonstrate the detectability of cold tumors using xSPECT technology compared with that of hot tumors in the phantom study. Five tumors of different sizes and normal bone contained a mixture of 99mTc and K2HPO4 in a spine phantom. We acquired SPECT data using an xSPECT protocol and transverse images were reconstructed using xSPECT Bone (xB) and xSPECT Quant (xQ). Mean standardized uptake values (SUVmean) in volumes of interest (VOI) were calculated. Recovery coefficients (RCs) for each tumor site were calculated with reference to radioactive concentrations. The SUVmeans of the whole vertebral body for hot tumor bone image in cortical bone phantom reconstructed by with xB and xQ were 5.77 and 4.86 respectively. The SUVmean of xB was similar to the true value. The SUVmeans for xB and xQ reconstructed images of cold tumors were both approximately 0.16. The RC of the cold tumor on xQ images increased as the tumor diameter decreased, whereas that of xB remained almost constant regardless of the tumor diameter. In conclusion, the quantitative accuracy of detecting hot and cold tumors was higher in the xB image than in the xQ image. Moreover, the visual detectability of cold tumors was also excellent in xB images.

Roles of histone H3K9 methyltransferases during Drosophila spermatogenesis.

Epigenetic regulation of gene expression by covalent modification of histones is important for germ line cell development. In mammals, histone H3 lysine 9 (H3K9)-specific histone methyltransferases (HMTases), such as G9a, SETDB1, and SUV39H, play critical roles, but the contribution of H3K9-specific HMTases in Drosophila remains to be clarified, especially in male sperm. Here, we performed immunocytochemical analyses with a specific antibody to dG9a, Drosophila G9a ortholog, and demonstrated localization in the cytoplasm from the growth to elongation stages of spermatogenesis. In the subsequent early canoe stage, strong dG9a signals were detected exclusively in nuclei, suggesting a regulatory role. However, mono-, di-, and trimethylated H3K9 signals were not extensively decreased in a homozygous dG9a null mutant throughout these stages. In contrast, mono- and trimethylated H3K9 signals were extensively decreased in a heterozygous DmSetdb1 mutant during spermatogenesis, and similar reduction in monomethylated H3K9 signals was observed in a homozygous Su(var)3-9 mutant. Therefore, DmSETDB1 is likely to be mainly responsible for mono- and trimethylation of H3K9 and SU(VAR)3-9 for monomethylation of H3K9 during spermatogenesis. However, the reduced methylation of H3K9 in premeiotic spermatocytes did not influence X-Y chromosome disjunction in male meiosis, suggesting that it may not be critical for spermatogenesis in Drosophila.

Prototype imaging protocols for monitoring the efficacy of iodine-131 ablation in differentiated thyroid cancer.

Whole-body and single photon emission tomography (SPET) images during sodium iodide-131 (Na131I) ablation are useful to confirm the efficacy of ablation using 131I imaging. However, there have been no attempts to improve the quality of 131I imaging. We therefore investigated imaging protocols for 131I imaging in differentiated thyroid cancer (DTC). Phantoms containing 131I were used to simulate extra-thyroid beds and thyroid beds. To simulate extra-thyroid beds, a phantom containing 0.19, 0.37, 0.74 or 1.85 MBq was placed in the acquisition center. To simulate the thyroid beds, four phantoms were applied as normal thyroid tissue, and four phantoms containing 0.19, 0.37, 0.74 and 1.85 MBq were arranged around normal thyroid tissue as a cancer. Whole-body imaging was performed at different table speeds, and SPET data acquired with various pixel sizes were reconstructed using a filtered backed projection (FBP) and ordered-subsets expectation maximization with 3-dimensional (OSEM-3D) algorithm. We measured full width at half maximum (FWHM) and % coefficient of variation (%CV). Patients were then examined based on the results of phantom studies. In extrathyroid beds, slower table speed in whole-body imaging improved %CV, but had little effect on FWHM. For SPET imaging OSEM-3D produced high-resolution and low-noise images, and FWHM and %CV improved with smaller pixel size, as compared with FBP. In the thyroid beds, only the 1.85 MBq phantom could be confirmed on whole-body imaging. Images by SPET had high FWHM and low %CV when the smaller pixel size and OSEM-3D were applied. Accumulation of ≤1.85 MBq was detected with a smaller pixel size of ≤4.8 mm and OSEM-3D. For Na131I ablation imaging, slower scan speed is suitable for whole-body imaging and smaller pixel size and OSEM-3D is appropriate for SPET imaging. In conclusion, we confirmed Na131I accumulation in thyroid beds using slower scan speed (≤15 cm/min) on whole-body imaging, and then accurate identification of Na131I accumulation using SPET and CT fusion imaging with smaller pixel size (≤4.8 mm) and OSEM-3D.

Dysfunctional Pro1 leads to female sterility in rice blast fungi.

Although sexual reproduction is widespread in eukaryotes, some fungal species can only reproduce asexually. In the rice blast fungus Pyricularia (Magnaporthe) oryzae, several isolates from the region of origin retain mating ability, but most isolates are female sterile. Therefore, female fertility may have been lost during its spread from the origin. Here, we show that functional mutations of Pro1, a global transcriptional regulator of mating-related genes in filamentous fungi, is one cause of loss of female fertility in this fungus. We identified the mutation of Pro1 by backcrossing analysis between female-fertile and female-sterile isolates. The dysfunctional Pro1 did not affect the infection processes but conidial release was increased. Furthermore, various mutations in Pro1 were detected in geographically distant P. oryzae, including pandemic isolates of wheat blast fungus. These results provide the first evidence that loss of female fertility may be advantageous to the life cycle of some plant pathogenic fungi.