Improving Visualization of In-stent Lumen Using Prototype Photon-counting Detector Computed Tomography with High-resolution Plaque Kernel.

The study aimed to compare the performance of photon-counting detector computed tomography (PCD CT) with high-resolution (HR)-plaque kernel with that of the energy-integrating detector CT (EID CT) in terms of the visualization of the lumen size and the in-stent stenotic portion at different coronary vessel angles. The lumen sizes in PCD CT and EID CT images were 2.13 and 1.80 mm at 0°, 2.20 and 1.77 mm at 45°, and 2.27 mm and 1.67 mm at 90°, respectively. The lumen sizes in PCD CT with HR-plaque kernel were wider than those in EID CT. The mean degree of the in-stent stenotic portion at 50% was 69.7% for PCD CT and 90.4% for EID CT. PCD CT images with HR-plaque kernel enable improved visualization of lumen size and accurate measurements of the in-stent stenotic portion compared to conventional EID CT images regardless of the stent direction.

Inverse correlation between age of onset and myocardial amyloid deposition quantified by 99mTc-PYP scintigraphy in patients with wild-type transthyretin amyloid cardiomyopathy.

OBJECTIVE: Wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt-CM) is increasingly recognized as a contributing factor to cardiac insufficiency in the elderly population. We aimed to identify the factors affecting age of onset of ATTRwt-CM, encompassing the assessment of amyloid deposition in myocardial tissue through the use of 99mTc-pyrophosphate (PYP) and clinical parameters. METHODS: A retrospective investigation involving a consecutive cohort of 107 cases, each having been diagnosed with ATTRwt-CM confirmed through histopathological and genetic analysis, was performed. All patients underwent PYP scintigraphy, and the heart-to-contralateral (H/CL) ratio was calculated to measure amyloid deposition in the myocardium. Univariate and multivariate analyses were performed to identify independent predictors of the age of onset of ATTRwt-CM, considering the H/CL ratio and various clinical risk factors for heart failure. RESULTS: Gender (p = 0.03), Creatinine (Cr) (r = 0.32, p < 0.01), hemoglobin (Hb) (r = - 0.44, p < 0.01), albumin (Alb) (r = - 0.32, p < 0.01), brain natriuretic peptide (BNP) (r = 0.21, p = 0.03), low-density lipoprotein-cholesterol (LDL-C) (r = - 0.27, p < 0.01), and H/CL ratio (r = - 0.44, p < 0.01) were all significantly associated with the onset age. In multiple regression analysis, the independent predictive factors for the onset age of ATTRwt-CM were identified as the H/CL ratio (p < 0.01), Hb (p < 0.01), and Cr (p < 0.01). CONCLUSION: The H/CL ratio, Hb, and Cr independently affect age of onset in patients with ATTRwt-CM. The H/CL ratio is inversely correlated with age of onset, and may be the sole factor in the development of heart failure in early onset patients, while it may have a synergistic effect on heart failure with anemia and renal dysfunction in late-onset patients.

Super-resolution deep-learning reconstruction for cardiac CT: impact of radiation dose and focal spot size on task-based image quality.

This study aimed to evaluate the impact of radiation dose and focal spot size on the image quality of super-resolution deep-learning reconstruction (SR-DLR) in comparison with iterative reconstruction (IR) and normal-resolution DLR (NR-DLR) algorithms for cardiac CT. Catphan-700 phantom was scanned on a 320-row scanner at six radiation doses (small and large focal spots at 1.4-4.3 and 5.8-8.8 mGy, respectively). Images were reconstructed using hybrid-IR, model-based-IR, NR-DLR, and SR-DLR algorithms. Noise properties were evaluated through plotting noise power spectrum (NPS). Spatial resolution was quantified with task-based transfer function (TTF); Polystyrene, Delrin, and Bone-50% inserts were used for low-, intermediate, and high-contrast spatial resolution. The detectability index (d') was calculated. Image noise, noise texture, edge sharpness of low- and intermediate-contrast objects, delineation of fine high-contrast objects, and overall quality of four reconstructions were visually ranked. Results indicated that among four reconstructions, SR-DLR yielded the lowest noise magnitude and NPS peak, as well as the highest average NPS frequency, TTF50%, d' values, and visual rank at each radiation dose. For all reconstructions, the intermediate- to high-contrast spatial resolution was maximized at 4.3 mGy, while the lowest noise magnitude and highest d' were attained at 8.8 mGy. SR-DLR at 4.3 mGy exhibited superior noise performance, intermediate- to high-contrast spatial resolution, d' values, and visual rank compared to the other reconstructions at 8.8 mGy. Therefore, SR-DLR may yield superior diagnostic image quality and facilitate radiation dose reduction compared to the other reconstructions, particularly when combined with small focal spot scanning.

Clinical characteristics of patients with high extracellular volume fraction evaluated by cardiac computed tomography for coronary artery evaluation.

Aims: This study aims to evaluate the distribution of extracellular volume fraction detected via computed tomography, clinical characteristics of high extracellular volume fraction detected via computed tomography, and the rate of incidental detection of cardiac amyloidosis in patients undergoing cardiac computed tomography for coronary artery evaluation. Methods and results: This study included 874 consecutive patients (mean age, 74.4 ± 7.1 years; men, 65%), comprising men aged ≥60 years and women aged ≥70 years, who had undergone cardiac computed tomography between January 2020 and September 2022. The mean extracellular volume fraction detected via computed tomography was 29.7 ± 5.2%, and 108 patients (12.4%) had an extracellular volume fraction detected via computed tomography of ≥35%. Older age (75.9 ± 8.2 years vs. 74.2 ± 6.9 years; P = 0.042), male sex (75.9% vs. 63.0%; P = 0.007), impaired left ventricular ejection fraction, increased high-sensitivity cardiac troponin T and B-type natriuretic peptide levels, and increased left ventricular thickness showed significant associations with an extracellular volume fraction detected via computed tomography of ≥35%. Cardiac amyloidosis was diagnosed incidentally in 15 patients based on an increase in extracellular volume fraction detected via computed tomography. The prevalence of cardiac amyloidosis was 1.7% (15/874) and 14.3% (15/105) in the entire study population and in patients with an extracellular volume fraction detected via computed tomography of ≥35%, respectively. An increase in the extracellular volume fraction detected via computed tomography was suggestive of cardiac amyloidosis. Conclusion: Elevated extracellular volume fraction detected via computed tomography, associated with elevated cardiac biomarker levels and myocardial structural changes, may lead to the incidental diagnosis of cardiac amyloidosis.

Diagnostic performance of unenhanced electrocardiogram-gated cardiac CT for detecting myocardial edema.

To assess the diagnostic performance of unenhanced electrocardiogram (ECG)-gated cardiac computed tomography (CT) for detecting myocardial edema, using MRI T2 mapping as the reference standard. This retrospective study protocol was approved by our institutional review board, which waived the requirement for written informed consent. Between December 2017 to February 2019, consecutive patients who had undergone T2 mapping for myocardial tissue characterization were identified. We excluded patients who did not undergo unenhanced ECG-gated cardiac CT within 3 months from MRI T2 mapping or who had poor CT image quality. All patients underwent unenhanced ECG-gated cardiac CT with an axial scan using a third-generation, 320 × 0.5 mm detector-row CT unit. Two radiologists together drew regions of interest (ROIs) in the interventricular septum on the unenhanced ECG-gated cardiac CT images. Using T2 mapping as the reference standard, the diagnostic performance of unenhanced cardiac CT for detecting myocardial edema was evaluated by using the area under the receiver operating characteristic curve with sensitivity and specificity. Youden index was used to find an optimal sensitivity-specificity cutoff point. A cardiovascular radiologist independently performed the measurements, and interobserver reliability was assessed using intraclass correlation coefficients for CT value measurements. A P value of <.05 was considered statistically significant. We included 257 patients who had undergone MRI T2 mapping. Of the 257 patients, 35 patients underwent unenhanced ECG-gated cardiac CT. One patient was excluded from the study because of poor CT image quality. Finally, 34 patients (23 men; age 64.7 ±â€…14.6 years) comprised our study group. Using T2 mapping, we identified myocardial edema in 19 patients. Mean CT and T2 values for 34 patients were 46.3 ±â€…2.7 Hounsfield unit and 49.0 ±â€…4.9 ms, respectively. Mean CT values moderately correlated with mean T2 values (Rho = -0.41; P < .05). Mean CT values provided a sensitivity of 63.2% and a specificity of 93.3% for detecting myocardial edema, with a cutoff value of ≤45.0 Hounsfield unit (area under the receiver operating characteristic curve = 0.77; P < .01). Inter-observer reproducibility in measuring mean CT values was excellent (intraclass correlation coefficient = 0.93; [95% confidence interval: 0.86, 0.96]). Myocardial edema could be detected by CT value of myocardium in unenhanced ECG-gated cardiac CT.

Human epididymis protein 4 is a useful predictor of post-operative prognosis in patients with severe aortic stenosis.

AIMS: The human epididymis protein 4 (HE4), a novel fibrosis marker, is expressed only in activated fibroblasts and is thought to reflect ongoing left ventricular (LV) fibrosis. LV fibrosis is a feature of severe aortic stenosis (AS) and is related to the post-operative outcome of patients with AS. We investigated the relationship between serum levels of HE4 and the post-operative prognosis of patients with severe AS. METHODS AND RESULTS: We measured the serum HE4 levels of 55 participants (80.8 ± 8.0 years old, male n = 26, 46%) with severe AS prior to surgical aortic valve replacement (n = 31, 56%) or transcatheter aortic valve implantation (n = 24, 44%) at Kumamoto University Hospital in 2018. We followed them for cardiovascular (CV) death or hospitalization for heart failure (HF) for 3 years. Serum HE4 levels were positively correlated with computed tomography-extracellular volume (CT-ECV) values (r = 0.53, P = 0.004). Kaplan-Meier curves demonstrated a significantly higher probability of hospitalization for HF or CV-related death in the patients with high HE4 (greater than the median HE4 value) compared with the patients with low HE4 (lower than the median HE4 value) (log-rank P = 0.003). Multivariate analysis showed HE4 (log(HE4)) to be an independent prognostic factor [hazard ratio (HR): 7.50; 95% confidence interval (CI): 1.81-31.1; P = 0.005]. Receiver operating characteristic (ROC) curve analysis suggested that HE4 is a marker of increased risk of CV-related death or hospitalization for HF at 3 years after surgery, with an area under the curve (AUC) of 0.76 (95% CI: 0.62-0.90; P = 0.003). CONCLUSIONS: We found that HE4 is a potentially useful biomarker for predicting future CV events in patients scheduled for AS surgery. Measuring serum HE4 values could help consider AS surgery.

A Novel Approach to Detecting Contrast Extravasation in Computed Tomography: Evaluating the Injection Pressure-to-Injection Rate Ratio.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of the injection pressure-to-injection rate (IPIR) ratio for the early detection of contrast extravasation at the venipuncture site during contrast-enhanced computed tomography. METHODS: We retrospectively enrolled 57,528 patients who underwent contrast-enhanced computed tomography examinations in a single hospital. The power injector recorded the contrast injection pressure at 0.25-second intervals. We constructed logistic regression models using the IPIR ratio as the independent variable and extravasation occurrence as the dependent variable (IPIR ratio models) at 1, 2, 3, 4, 5, and 6 seconds after the start of contrast administration. Univariate logistic regression models in which injection pressure is used as an independent variable (injection pressure models) were also constructed as a reference baseline. The performance of the models was evaluated with the area under the receiver operating characteristic curves. RESULTS: Of the 57,528 cases, 46,022 were assigned to the training group and 11,506 were assigned to the test group, which included 112 extravasation cases (0.24%) in the training group and 28 (0.24%) in the test group. The area under the receiver operating characteristic curves for the IPIR ratio models and injection pressure models were 0.555 versus 0.563 at t = 1 (P = 0.270), 0.712 versus 0.678 at t = 2 (P = 0.305), 0.758 versus 0.693 at t = 3 (P = 0.032), 0.776 versus 0.688 at t = 4 (P = 0.005), 0.810 versus 0.699 at t = 5 (P = 0.002), and 0.811 versus 0.706 at t = 6 (P = 0.002). CONCLUSIONS: The IPIR ratio models perform better in detecting contrast extravasation at 3 to 6 seconds after the start of contrast administration than injection pressure models.

Low tube voltage and deep-learning reconstruction for reducing radiation and contrast medium doses in thin-slice abdominal CT: a prospective clinical trial.

OBJECTIVES: To investigate the feasibility of low-radiation dose and low iodinated contrast medium (ICM) dose protocol combining low-tube voltage and deep-learning reconstruction (DLR) algorithm in thin-slice abdominal CT. METHODS: This prospective study included 148 patients who underwent contrast-enhanced abdominal CT with either 120-kVp (600 mgL/kg, n = 74) or 80-kVp protocol (360 mgL/kg, n = 74). The 120-kVp images were reconstructed using hybrid iterative reconstruction (HIR) (120-kVp-HIR), while 80-kVp images were reconstructed using HIR (80-kVp-HIR) and DLR (80-kVp-DLR) with 0.5 mm thickness. Size-specific dose estimate (SSDE) and iodine dose were compared between protocols. Image noise, CT attenuation, and contrast-to-noise ratio (CNR) were quantified. Noise power spectrum (NPS) and edge rise slope (ERS) were used to evaluate noise texture and edge sharpness, respectively. The subjective image quality was rated on a 4-point scale. RESULTS: SSDE and iodine doses of 80-kVp were 40.4% (8.1 ± 0.9 vs. 13.6 ± 2.7 mGy) and 36.3% (21.2 ± 3.9 vs. 33.3 ± 4.3 gL) lower, respectively, than those of 120-kVp (both, p < 0.001). CT attenuation of vessels and solid organs was higher in 80-kVp than in 120-kVp images (all, p < 0.001). Image noise of 80-kVp-HIR and 80-kVp-DLR was higher and lower, respectively than that of 120-kVp-HIR (both p < 0.001). The highest CNR and subjective scores were attained in 80-kVp-DLR (all, p < 0.001). There were no significant differences in average NPS frequency and ERS between 120-kVp-HIR and 80-kVp-DLR (p ≥ 0.38). CONCLUSION: Compared with the 120-kVp-HIR protocol, the combined use of 80-kVp and DLR techniques yielded superior subjective and objective image quality with reduced radiation and ICM doses at thin-section abdominal CT. CLINICAL RELEVANCE STATEMENT: Scanning at low-tube voltage (80-kVp) combined with the deep-learning reconstruction algorithm may enhance diagnostic efficiency and patient safety by improving image quality and reducing radiation and contrast doses of thin-slice abdominal CT. KEY POINTS: Reducing radiation and iodine doses is desirable; however, contrast and noise degradation can be detrimental. The 80-kVp scan with the deep-learning reconstruction technique provided better images with lower radiation and contrast doses. This technique may be efficient for improving diagnostic confidence and patient safety in thin-slice abdominal CT.

Cardiac Biomarker Change at 1 Year After Tafamidis Treatment and Clinical Outcomes in Patients With Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: Although tafamidis treatment improves prognosis in patients with wild-type transthyretin amyloid cardiomyopathy, an optimal surrogate marker monitoring its therapeutic effect remains unclear. This study investigated the association between changes in cardiac biomarkers, high-sensitivity cardiac troponin T (hs-cTnT) and B-type natriuretic peptide (BNP) during the first year after tafamidis treatment and clinical outcomes. METHODS AND RESULTS: In 101 patients with wild-type transthyretin amyloid cardiomyopathy receiving tafamidis at our institution, change in cardiac biomarkers from baseline to 1 year after tafamidis administration and its association with composite outcomes (composite of all-cause death and hospitalization attributable to heart failure) was assessed. During the follow-up period (median, 17 months), 16 (16%) patients experienced composite outcomes. The hs-cTnT level significantly decreased at 1 year after tafamidis treatment, unlike the BNP level. The frequencies of increased hs-cTnT and BNP levels were significantly higher in those with composite outcomes than in those without (44% versus 15%; P=0.01). Kaplan-Meier survival analysis showed that patients in whom both hs-cTnT and BNP levels increased at 1 year after tafamidis had a higher probability of composite outcomes compared with those with decreased hs-cTnT and BNP levels (log-rank P<0.01). Cox regression analysis identified increased hs-cTnT and BNP levels at 1 year after tafamidis administration as an independent predictor of higher cumulative risk of composite outcomes. CONCLUSIONS: Deterioration in cardiac biomarkers during the first year after tafamidis treatment predicted a worse prognosis, suggesting the utility of serial assessment of cardiac biomarkers for monitoring the therapeutic response to tafamidis in patients with wild-type transthyretin amyloid cardiomyopathy.

Transarterial Embolization of Renal Arteriovenous Malformations: Treatment Outcomes According to Angiographic Classification.

PURPOSE: To assess the different adjunctive catheter techniques required to achieve complete occlusion of renal arteriovenous malformations (rAVMs) of different angioarchitectural types. MATERIALS AND METHODS: Overall, data on 18 patients with rAVM (Type 1, n = 7; Type 2, n = 2; Type 3, n = 9; mean age, 53.8 years) who underwent 25 procedures between 2011 and 2022 were reviewed. The clinical presentations, endovascular techniques, arteriovenous malformation (AVM) occlusion rate, adverse events (including the incidence of renal infarction), and clinical symptoms and outcomes (including recurrence/increase of AVM) were analyzed according to the Cho-Do angioarchitectural classification. Posttreatment renal infarction was classified as no infarction, small infarction (<12.5%), medium infarction (12.5%-25%), and large infarction (>25%) using contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: Hematuria and heart failure were presenting symptoms in 10 and 2 patients, respectively. The embolic materials used were as follows: Type 1 rAVM, coils alone or with n-butyl-2-cyanoacrylate (nBCA); Type 2 rAVM, nBCA alone or with coils; and Type 3 rAVMs, nBCA alone. Fourteen patients underwent adjunctive catheter techniques, including flow control with a balloon catheter and multiple microcatheter placement, alone or in combination. Immediate postprocedural angiography revealed complete occlusion in 15 patients (83%) and marked regression of rAVM in 3 (17%). Small asymptomatic renal infarctions were observed in 6 patients with Type 3 rAVMs without any decrease in renal function. No major adverse events were observed. All symptomatic patients experienced symptom resolution. Recurrence/increase of rAVM was not observed during the mean 32-month follow-up period (range, 2-120 months). CONCLUSIONS: Transarterial embolization using adjunctive catheter techniques according to angioarchitectural types can be an effective treatment for rAVMs.

Diagnostic performance of hepatic CT and chemical-shift MRI to discriminate lipid-poor adrenal adenomas from hepatocellular carcinoma metastases.

PURPOSE: To evaluate the diagnostic performance of multiphase hepatic CT parameters (non-contrast attenuation, absolute and relative washout ratios [APW and RPW, respectively], and relative enhancement ratio [RER]) and chemical-shift MRI (CS-MRI) for discriminating lipid-poor adrenal adenomas (with non-contrast CT attenuation > 10 HU) from metastases in patients with hepatocellular carcinoma (HCC). METHODS: This retrospective study included HCC patients with lipid-poor adrenal lesions who underwent multiphase hepatic CT between January 2010 and December 2021. For each adrenal lesion, non-contrast attenuation, APW, RPW, RER, and signal-intensity index (SI-index) were measured. Each parameter was compared between adenomas and metastases. The area under the receiver operating characteristic curves (AUCs) and sensitivities to achieve 100% specificity for adenoma diagnoses were determined. RESULTS: 104 HCC patients (78 men; mean age, 71.8 ± 9.6 years) with 63 adenomas and 48 metastases were identified; CS-MRI was performed in 66 patients with 49 adenomas and 21 metastases within one year of CT. Lipid-poor adenomas showed lower non-contrast attenuation (22.9 ± 7.1 vs. 37.9 ± 9.4 HU) and higher APW (40.5% ± 12.8% vs. 23.7% ± 17.4%), RPW (30.0% ± 10.2% vs. 12.4% ± 9.6%), RER (329% ± 152% vs. 111% ± 43.0%), and SI-index (43.3 ± 20.7 vs. 10.8 ± 13.4) than HCC metastases (all p < .001). AUC for non-contrast attenuation, APW, RPW, RER, and SI-index were 0.894, 0.786, 0.904, 0.969, and 0.902, respectively. The sensitivities to achieve 100% specificity were 7.9%, 25.4%, 30.2%, 63.5%, and 24.5%, respectively. Combined RER and APW achieved the highest sensitivity of 73.0%. CONCLUSION: Multiphase hepatic CT allows for better discrimination between lipid-poor adrenal adenomas and metastases relative to CS-MRI, especially when combined with RER and washout parameters.

Effect of deep learning-based reconstruction on high-resolution three-dimensional T2-weighted fast asymmetric spin-echo imaging in the preoperative evaluation of cerebellopontine angle tumors.

PURPOSE: We aimed to evaluate the effect of deep learning-based reconstruction (DLR) on high-spatial-resolution three-dimensional T2-weighted fast asymmetric spin-echo (HR-3D T2-FASE) imaging in the preoperative evaluation of cerebellopontine angle (CPA) tumors. METHODS: This study included 13 consecutive patients who underwent preoperative HR-3D T2-FASE imaging using a 3 T MRI scanner. The reconstruction voxel size of HR-3D T2-FASE imaging was 0.23 × 0.23 × 0.5 mm. The contrast-to-noise ratios (CNRs) of the structures were compared between HR-3D T2-FASE images with and without DLR. The observers' preferences based on four categories on the tumor side on HR-3D T2-FASE images were evaluated. The facial nerve in relation to the tumor on HR-3D T2-FASE images was assessed with reference to intraoperative findings. RESULTS: The mean CNR between the tumor and trigeminal nerve and between the cerebrospinal fluid and trigeminal nerve was significantly higher for DLR images than non-DLR-based images (14.3 ± 8.9 vs. 12.0 ± 7.6, and 66.4 ± 12.0 vs. 53.9 ± 8.5, P < 0.001, respectively). The observer's preference for the depiction and delineation of the tumor, cranial nerves, vessels, and location relation on DLR HR-3D T2FASE images was superior to that on non-DLR HR-3D T2FASE images in 7 (54%), 6 (46%), 6 (46%), and 6 (46%) of 13 cases, respectively. The facial nerves around the tumor on HR-3D T2-FASE images were visualized accurately in five (38%) cases with DLR and in four (31%) without DLR. CONCLUSION: DLR HR-3D T2-FASE imaging is useful for the preoperative assessment of CPA tumors.

Optimizing High-Resolution MR Angiography: The Synergistic Effects of 3D Wheel Sampling and Deep Learning-Based Reconstruction.

OBJECTIVE: The aim of this study was to assess the utility of the combined use of 3D wheel sampling and deep learning-based reconstruction (DLR) for intracranial high-resolution (HR)-time-of-flight (TOF)-magnetic resonance angiography (MRA) at 3 T. METHODS: This prospective study enrolled 20 patients who underwent head MRI at 3 T, including TOF-MRA. We used 3D wheel sampling called "fast 3D" and DLR for HR-TOF-MRA (spatial resolution, 0.39 × 0.59 × 0.5 mm3) in addition to conventional MRA (spatial resolution, 0.39 × 0.89 × 1 mm3). We compared contrast and contrast-to-noise ratio between the blood vessels (basilar artery and anterior cerebral artery) and brain parenchyma, full width at half maximum in the P3 segment of the posterior cerebral artery among 3 protocols. Two board-certified radiologists evaluated noise, contrast, sharpness, artifact, and overall image quality of 3 protocols. RESULTS: The contrast and contrast-to-noise ratio of fast 3D-HR-MRA with DLR are comparable or higher than those of conventional MRA and fast 3D-HR-MRA without DLR. The full width at half maximum was significantly lower in fast 3D-MRA with and without DLR than in conventional MRA (P = 0.006, P < 0.001). In qualitative evaluation, fast 3D-MRA with DLR had significantly higher sharpness and overall image quality than conventional MRA and fast 3D-MRA without DLR (sharpness: P = 0.021, P = 0.001; overall image quality: P = 0.029, P < 0.001). CONCLUSIONS: The combination of 3D wheel sampling and DLR can improve visualization of arteries in intracranial TOF-MRA.

Safety and dose-finding trial of tadalafil administered for fetus in labor: A phase I clinical study.

AIM: This study aimed to investigate the safety and efficacy of tadalafil in protecting the fetus from hypoxic stress caused by repeated labor pains during delivery and preventing fetal hypoxic-ischemic encephalopathy. METHODS: The study used a three-case cohort approach. Three patients were administered 10 mg tadalafil and monitored for serious adverse events. In the absence of serious tadalafil-associated adverse events as assessed by the Safety Evaluation Committee, three new patients were added to the study and treated with 20 mg/dose. The blood levels of tadalafil were recorded before and after 2, 4, 8, and 12 h of administration and 2 h after delivery. RESULTS: A total of seven patients were enrolled, and after excluding one patient who delivered before 37 weeks, tadalafil was administered to six patients. Maternal adverse events were considered acceptable from the maternal perspective, with grade 1 headache, anorexia, and myalgia and no obstetrical complications after delivery at both doses. No serious neonatal adverse events were associated with tadalafil. Tadalafil blood levels remained stable at both doses. In addition, the level of soluble fms-like tyrosine kinase-1 did not alter, while that of the placental growth factor differed significantly before and after tadalafil administration. CONCLUSIONS: The study confirmed the safety of tadalafil administration during delivery for both mothers and newborns. The stable tadalafil blood levels confirmed the efficacy of the tested administration regime at 12 h interval. These findings would assist in conducting phase II trials to further verify the optimal dose and safety of tadalafil.

Long-term outcomes of multidisciplinary treatment combining surgery and stereotactic radiotherapy with Novalis for craniopharyngioma.

Craniopharyngiomas are difficult to resect completely, recurrence is frequent, and hypothalamic/pituitary function may be affected after surgery. Therefore, the ideal treatment for craniopharyngiomas is local control with preservation of hypothalamic and pituitary functions. The purpose of this study is to retrospectively evaluate the long-term efficacy and adverse events of stereotactic radiotherapy (SRT) with Novalis for craniopharyngioma. This study included 23 patients with craniopharyngiomas who underwent surgery between 2006 and 2021 and underwent SRT as their first irradiation after surgery. The median post-irradiation observation period was 88 months, with the overall survival rates of 100 % at 10 years and 85.7 % at 20 years. One patient died of adrenal insufficiency 12 years after irradiation. The local control rate of the cystic component was 91.3 % at 5 years, 83.0 % at 15 years, with no increase in the solid component. No delayed impairment of visual or pituitary function due to irradiation was observed. No new hypothalamic dysfunction was observed after radiation therapy. No delayed adverse events such as brain necrosis, cerebral artery stenosis, cerebral infarction, or secondary brain tumors were also observed. SRT was safe and effective over the long term in patients irradiated in childhood as well as adults, with no local recurrence or adverse events. We believe that surgical planning for craniopharyngioma with stereotactic radiotherapy in mind is effective in maintaining a good prognosis and quality of life.

Postoperative disappearance of leptomeningeal enhancement around the brainstem in glioblastoma.

PURPOSE: Leptomeningeal enhancement (LME) suggests leptomeningeal dissemination (LMD) of tumor cells, which is a complication of end-stage glioblastoma, and is associated with a poor prognosis. However, magnetic resonance imaging (MRI) occasionally indicates the disappearance of peri-brainstem LME after surgical resection of glioblastoma. Since preoperative LMD may affect treatment indications, we aimed to analyze the clinical significance of preoperative LME of the brainstem in glioblastoma. METHODS: We retrospectively collected clinical and radiological data from consecutive patients with glioblastoma and preoperative LME of the brainstem, who were treated at our hospital between 2017 and 2020. RESULTS: Among 112 patients with glioblastoma, nine (8%) showed preoperative LME of the brainstem. In comparison with tumors without LME, tumor size was significantly associated with the preoperative LME of the brainstem (p = 0.016). In addition, there was a trend toward significance for a relationship between deep tumor location and preoperative LME of the brainstem (p = 0.058). Notably, among six patients who underwent surgical resection for glioblastoma with LME of the brainstem, four showed significant radiological disappearance of the LME on postoperative MRI. This suggests that the LME did not result from LMD in these cases. Moreover, these four patients lived longer than would be expected from the presence of LMD. However, this LME disappearance was not observed after biopsy or chemoradiotherapy. CONCLUSIONS: These findings suggest that preoperative LME does not necessarily indicate the presence of untreatable LMD; moreover, LME may disappear after surgical tumor resection. Thus, transient preoperative LME could be attributed to other mechanisms, including impaired venous flow due to intratumoral arteriovenous shunts, which can be resolved by reducing the tumor burden.

A Rare Case of Adult Poorly Differentiated Chordoma of the Skull Base With Rapid Progression and Systemic Metastasis: A Review of the Literature.

Chordoma is a rare tumor that arises from chordal tissue during fetal life. Recently, the concept of poorly differentiated chordoma, a subtype of chordoma characterized by loss of SMARCB1/INI1 with a poorer prognosis than conventional chordomas, was established. It predominantly occurs in children and is rare in adults. Here, we report a rare adult case of poorly differentiated chordoma of the skull base with a unique course that rapidly systemically metastasized and had the shortest survival time of any adult chordoma reported to date. The patient was a 32-year-old male with a chief complaint of diplopia. MRI showed a widespread neoplastic lesion with the clivus as the main locus. Endoscopic extended transsphenoidal tumor resection was performed. Pathological findings showed that the tumor was malignant, and immunohistochemistry revealed a Ki-67 labeling index of 80%, diffusely positive brachyury, and loss of INI1 expression. The final diagnosis was poorly differentiated chordoma. Postoperatively, the residual tumor in the right cavernous sinus showed rapid growth. The patient was promptly treated with gamma knife three fractions. The residual tumor regressed, but the tumor developed systemic metastasis in a short period, and the patient died seven months after diagnosis. This report of a rapidly progressing and fatal adult poorly differentiated chordoma shows the highest Ki-67 labeling index reported to date. Prompt multidisciplinary treatment should be considered when the Ki-67 labeling index is high.

Myocardial extracellular volume quantification in cardiac amyloidosis: a comparative study between cardiac computed tomography and magnetic resonance imaging.

OBJECTIVES: Myocardial extracellular volume (ECV) on computed tomography (CT), an alternative to cardiac magnetic resonance (CMR), has significant practical clinical advantages. However, the consistency between ECVs quantified via CT and CMR in cardiac amyloidosis (CA) has not been investigated sufficiently. Therefore, the current study investigated the application of CT-ECV in CA with CMR-ECV as the reference standard. METHODS: We retrospectively evaluated 31 patients with CA who underwent cardiac CT and CMR. Pearson correlation analysis was performed to investigate correlations between CT-ECV and CMR-ECV at each segment. Further, correlations between ECV and clinical parameters were assessed. RESULTS: There were no significant differences in the mean global ECVs between CT scan and CMR (51.3% ± 10.2% vs 50.0% ± 10.5%). CT-ECV was correlated with CMR-ECV at the septal (r = 0.88), lateral (r = 0.80), inferior (r = 0.79), anterior (r = 0.77) segments, and global (r = 0.87). In both CT and CMR, the ECV had a weak to strong correlation with high-sensitivity cardiac troponin T level, a moderate correlation with global longitudinal strain, and an inverse correlation with left ventricular ejection fraction. Further, the septal ECV and global ECV had a slightly higher correlation with the clinical parameters. CONCLUSIONS: Cardiac CT can quantify myocardial ECV and yield results comparable to CMR in patients with CA. Moreover, a significant correlation between CT-ECV and clinical parameters was observed. Thus, CT-ECV can be an imaging biomarker and alternative to CMR-ECV. CLINICAL RELEVANCE STATEMENT: Cardiac CT can quantify myocardial ECV and yield results comparable to CMR in patients with CA, and CT-ECV can be used clinically as an imaging biomarker and alternative to CMR-ECV. KEY POINTS: • A significant correlation was found between CT myocardial extracellular volume and cardiac MR myocardial extracellular volume in patients with cardiac amyloidosis. • In CT and cardiac MR, the myocardial extracellular volume correlated well with high-sensitivity cardiac troponin T level, global longitudinal strain, and left ventricular ejection fraction. • CT myocardial extracellular volume can be an imaging biomarker and alternative to cardiac MR myocardial extracellular volume.

Kinetic-pharmacodynamic model of warfarin for prothrombin time-international normalized ratio in Japanese patients.

AIMS: Genotype-guided dosing algorithms can explain about half of the interindividual variability in prothrombin time-international normalized ratio (PT-INR) under warfarin treatment. This study aimed to refine a published kinetic-pharmacodynamic model and guide warfarin dosage for an optimal PT-INR based on renal function. METHODS: Using a retrospective cohort of adult patients (>20 years) who were administered warfarin and underwent PT-INR measurements, we refined the kinetic-pharmacodynamic model with age and the genotypes of cytochrome P450 2C9 and vitamin K epoxide reductase complex subunit 1 using the PRIOR subroutine in the nonlinear-mixed-effect modelling programme. We searched the significant covariates for parameters, such as the dose rate for 50% inhibition of coagulation (EDR50 ), using a stepwise forward and backward method. Monte Carlo simulation determined a required daily dose of warfarin with a target range of PT-INR (2.0-3.0 or 1.6-2.6) based on the significant covariates. RESULTS: A total of 350 patients with 2762 PT-INR measurements were enrolled (estimated glomerular filtration rate [eGFR]: 47.5 [range: 2.6-199.0] mL/min/1.73 m2 ). The final kinetic-pharmacodynamic model showed that the EDR50 changed power functionally with body surface area, serum albumin level and eGFR. Monte Carlo simulation revealed that a lower daily dose of warfarin was required to attain the target PT-INR range as eGFR decreased. CONCLUSIONS: Model-informed precision dosing of warfarin is a valuable approach for estimating its dosage in patients with renal impairment.