Association Between Pretreatment 11C-Methionine Positron Emission Tomography Metrics, Histology, and Prognosis in 125 Newly Diagnosed Patients with Adult-Type Diffuse Glioma Based on the World Health Organization 2021Classification.

OBJECTIVE: To clarify the relationships between 11C-methionine (MET) positron emission tomography (PET) metrics and the histology, genetics, and prognosis of adult-type diffuse glioma (ADG) based on the World Health Organization (WHO) 2021 classification. METHODS: A total of 125 newly diagnosed patients with ADG were enrolled. We compared the maximum standardized uptake value (SUVmax), tumor-to-normal background ratio (TNR), metabolic tumor volume (MTV), and total lesion methionine uptake (TLMU) to the histology and genetics of the patients with ADG. We also evaluated the prognoses of the 93 surgically treated patients. RESULTS: The patients with isocitrate dehydrogenase wild ADG showed significantly higher MET-PET metrics (P < 0.05 for all parameters), significantly shorter overall survival and progression-free survival (P < 0.0001 for both) than those of the patients with isocitrate dehydrogenase mutant (IDHm) ADG. In the IDHm ADG group, the SUVmax, MTV, and TLMU values were significantly higher in patients with IDHm grade (G) 4 astrocytoma than patients with IDHm G2/3 astrocytoma (P < 0.05 for all), but not than patients with G2-3 oligodendroglioma. The progression-free survival was significantly shorter in the patients with G4 astrocytoma versus the patients with G2/3 astrocytoma and G3 oligodendroglioma (P < 0.05 for both). The SUVmax and TNR values were significantly higher in recurrent patients than nonrecurrent patients (P < 0.01 for both), but no significant differences were found in MTV or TLMU values. CONCLUSIONS: MET-PET metrics well reflect the histological subtype, WHO grade and prognosis of ADG based on the 2021 WHO classification, with the exception of oligodendroglial tumors. Volumetric parameters were not significantly associated with recurrence, unlike the SUVmax and TNR.

The International Association for the Study of Lung Cancer (IASLC) Staging Project for Lung Cancer: Recommendation to Introduce Spread Through Air Spaces as a Histologic Descriptor in the Ninth Edition of the TNM Classification of Lung Cancer. Analysis of 4061 Pathologic Stage I NSCLC.

INTRODUCTION: Spread through air spaces (STAS) consists of lung cancer tumor cells that are identified beyond the edge of the main tumor in the surrounding alveolar parenchyma. It has been reported by meta-analyses to be an independent prognostic factor in the major histologic types of lung cancer, but its role in lung cancer staging is not established. METHODS: To assess the clinical importance of STAS in lung cancer staging, we evaluated 4061 surgically resected pathologic stage I R0 NSCLC collected from around the world in the International Association for the Study of Lung Cancer database. We focused on whether STAS could be a useful additional histologic descriptor to supplement the existing ones of visceral pleural invasion (VPI) and lymphovascular invasion (LVI). RESULTS: STAS was found in 930 of 4061 of the pathologic stage I NSCLC (22.9%). Patients with tumors exhibiting STAS had a significantly worse recurrence-free and overall survival in both univariate and multivariable analyses involving cohorts consisting of all NSCLC, specific histologic types (adenocarcinoma and other NSCLC), and extent of resection (lobar and sublobar). Interestingly, STAS was independent of VPI in all of these analyses. CONCLUSIONS: These data support our recommendation to include STAS as a histologic descriptor for the Ninth Edition of the TNM Classification of Lung Cancer. Hopefully, gathering these data in the coming years will facilitate a thorough analysis to better understand the relative impact of STAS, LVI, and VPI on lung cancer staging for the Tenth Edition TNM Stage Classification.

Simultaneous evaluation of brain metastasis and thoracic cancer using semiconductor 11C-methionine PET/CT imaging.

OBJECTIVE: To investigate the potential of whole-body digital 11C-methionine (MET) PET/CT imaging for simultaneous evaluation of thoracic cancer patients suspected of local recurrence (LR) after stereotactic radiosurgery (SRS) for brain metastasis. METHODS: A total of 45 lung or breast cancer patients suspected of LR after SRS were investigated using brain and whole-body MET-PET/CT scans. We compared the tumor-to-normal ratio (TNR) and maximum standardized uptake values (SUVmax) between patients with LR and radiation necrosis (RN) and performed receiver operating characteristic (ROC) analyses. We also investigated associations among extracranial recurrence, intracranial recurrence, primary site, and initial treatment type. RESULTS: A total of 44 LR and 14 RN lesions were analyzed. In the ROC analyses for differentiating LR from RN, TNR showed higher area under the curve (AUC) (0.82) than SUVmax (0.79), and the cutoff TNR value (2.12) was higher than current cutoff values of conventional PET systems. The whole-body scans detected extracranial recurrences in 31.1% of the patients. Recurrence rates were not significantly correlated with existence of intracranial recurrence or primary site, but patients who underwent non-surgical treatment (consisting of stage III/ IV patients according to the Union for International Cancer Control TNM classification or small-cell lung cancer patients) showed significantly higher recurrence than the surgically treated patients (68.8% vs. 10.3%, p = 0.0001). CONCLUSION: In digital MET-PET/CT imaging, TNR was a more useful parameter to differentiate LR from RN than SUVmax, and the cutoff value was higher than those with conventional PET systems. Additional whole-body scans could detect extracranial recurrence and would be especially useful for advanced thoracic cancer patients who underwent non-surgical treatment.

Prognostic value of right atrial strain in systemic sclerosis based on tissue tracking analysis using cine cardiac magnetic resonance imaging: a retrospective observational study.

Interstitial lung disease and cardiac involvement are common manifestations and prognostic factors of systemic sclerosis. However, it is unclear whether impaired right atrial function associated with interstitial lung disease in systemic sclerosis can be used as a prognostic factor in this patient population. Therefore, this study aimed to investigate the relationship between right atrial function, interstitial lung disease, and prognosis in patients with systemic sclerosis using tissue tracking analysis with cine cardiac magnetic resonance imaging. In this retrospective observational study, a total of 40 patients with systemic sclerosis were enrolled. Tissue tracking analysis was used to obtain time curves of right atrial strain. Reservoir (total strain), conduit (passive strain), and booster (active strain) pump function were calculated, and right atrial strain, interstitial lung disease, and clinical outcomes were examined. An adverse clinical event was defined as all-cause death. Overall, 23 patients had interstitial lung disease (58%). Six patients died during the follow-up (median, 44 months). The total skin score and right ventricular systolic pressure on echocardiography were higher in patients with an event than in those without an event (28 ± 16% vs. 13 ± 13%, P = 0.02; 46.3 ± 10.7 mmHg vs. 36.0 ± 8.5 mmHg, P = 0.01, respectively). Further, right atrial total strain and active strain were significantly lower in patients with an event than in those without an event (14.3 ± 11.3% vs. 25.8 ± 11.4%, P = 0.03; 3.48 ± 2.37 vs. 11.7 ± 6.78, P = 0.007, respectively). Multivariate analysis revealed that active strain was an independent predictor of all-cause death (hazard ratio 0.76, P = 0.029). Kaplan-Meier analysis revealed that the survival rate was significantly higher in patients with right atrial active strain levels above the cutoff 7.4 (P < 0.05). In systemic sclerosis, right atrial booster function was predictive of mortality. Hence, right atrial functional assessment may have incremental prognostic value for patients with systemic sclerosis, leading to better risk stratification.

Patlak Reconstruction Using Dynamic 18 F-FDG PET Imaging for Evaluation of Malignant Liver Tumors : A Comparison of HCC, ICC, and Metastatic Liver Tumors.

PURPOSE OF THE REPORT: The aim of this study was to explore the different patterns of dynamic whole-body (D-WB) FDG PET/CT parameters among liver malignancy types as potential diagnostic clues and investigate the association between static and dynamic PET/CT parameters for each tumor histology. PATIENTS AND METHODS: Seventy-one patients with intrahepatic cholangiocarcinoma (ICC), metastatic liver tumor (MLT), or hepatocellular carcinoma (HCC) who underwent D-WB and static dual-time-point FDG PET/CT were enrolled. We obtained Pearson correlation coefficients between the metabolic rate of FDG (MR FDG ; mg/min/ 100ml) or distribution volume of free FDG (DV FDG , %) and static PET/CT parameters. We compared MR FDG and DV FDG values by tumor type and performed receiver operating characteristic analyses for MR FDG and static images. RESULTS: A total of 12 ICC, 116 MLT, and 36 HCC lesions were analyzed. MR FDG and DV FDG showed excellent correlation with early (SUV e ) and delayed SUV max (SUV d ) ( r = 0.71~0.97), but DV FDG in the HCC lesions did not ( r = 0.62 and 0.69 for SUV e and SUV d , respectively) ( P < 0.001 for all). HCC lesions showed significantly lower MR FDG (2.43 ± 1.98) and DV FDG (139.95 ± 62.58) than ICC (5.02 ± 3.56, 207.06 ± 97.13) and MLT lesions (4.51 ± 2.47, 180.13 ± 75.58) ( P < 0.01 for all). The optimal MR FDG could differentiate HCC from ICC and MLT with areas under the curve of 0.84 and 0.80, respectively. Metastatic liver tumor lesions showed the widest distribution of MR FDG and DV FDG values but with no significant difference among most primary sites. CONCLUSIONS: MR FDG was strongly correlated with SUV max in the 3 malignancies and showed utility for differentiating HCC from ICC and MLT. Each tumor type has a different glucose metabolism, and D-WB FDG PET/CT imaging has the potential to visualize those differences.

Deep learning approach using SPECT-to-PET translation for attenuation correction in CT-less myocardial perfusion SPECT imaging.

OBJECTIVE: Deep learning approaches have attracted attention for improving the scoring accuracy in computed tomography-less single photon emission computed tomography (SPECT). In this study, we proposed a novel deep learning approach referring to positron emission tomography (PET). The aims of this study were to analyze the agreement of representative voxel values and perfusion scores of SPECT-to-PET translation model-generated SPECT (SPECTSPT) against PET in 17 segments according to the American Heart Association (AHA). METHODS: This retrospective study evaluated the patient-to-patient stress, resting SPECT, and PET datasets of 71 patients. The SPECTSPT generation model was trained (stress: 979 image pairs, rest: 987 image pairs) and validated (stress: 421 image pairs, rest: 425 image pairs) using 31 cases of SPECT and PET image pairs using an image-to-image translation network. Forty of 71 cases of left ventricular base-to-apex short-axis images were translated to SPECTSPT in the stress and resting state (stress: 1830 images, rest: 1856 images). Representative voxel values of SPECT and SPECTSPT in the 17 AHA segments against PET were compared. The stress, resting, and difference scores of 40 cases of SPECT and SPECTSPT were also compared in each of the 17 segments. RESULTS: For AHA 17-segment-wise analysis, stressed SPECT but not SPECTSPT voxel values showed significant error from PET at basal anterior regions (segments #1, #6), and at mid inferoseptal regions (segments #8, #9, and #10). SPECT, but not SPECTSPT, voxel values at resting state showed significant error at basal anterior regions (segments #1, #2, and #6), and at mid inferior regions (segments #8, #9, and #11). Significant SPECT overscoring was observed against PET in basal-to-apical inferior regions (segments #4, #10, and #15) during stress. No significant overscoring was observed in SPECTSPT at stress, and only moderate over and underscoring in the basal inferior region (segment #4) was found in the resting and difference states. CONCLUSIONS: Our PET-supervised deep learning model is a new approach to correct well-known inferior wall attenuation in SPECT myocardial perfusion imaging. As standalone SPECT systems are used worldwide, the SPECTSPT generation model may be applied as a low-cost and practical clinical tool that provides powerful auxiliary information for the diagnosis of myocardial blood flow.

The International Association for the Study of Lung Cancer Lung Cancer Staging Project: Proposals for the Revisions of the T-Descriptors in the Forthcoming Ninth Edition of the TNM Classification for Lung Cancer.

INTRODUCTION: An international database was created by the International Association for the Study of Lung Cancer to inform on the ninth edition of the TNM classification of lung cancer. The present analyses concern its T component. METHODS: Data on 124,581 patients diagnosed with lung cancer from January 1, 2011 to December 31, 2019 were submitted to the International Association for the Study of Lung Cancer database. Of these, 33,982 met the inclusion criteria for the clinical T analysis, and 30,715 met the inclusion criteria for the pathologic postsurgical analysis. Survival was measured from the date of diagnosis or operation for clinically and pathologically staged tumors, respectively. T descriptors were evaluated in univariate analysis and multivariable Cox regression analysis adjusted for age, sex, pathologic type, and geographic region. RESULTS: Comprehensive survival analysis revealed that the existing eighth edition T component criteria performed adequately in the ninth edition data set. Although pathologic chest wall or parietal pleura involvement (PL 3) yielded a worse survival compared with the other T3 descriptors, with a similar survival as T4 tumors, this difference was not observed for clinical chest wall or PL 3 tumors. Because of these inconsistent findings, no reallocation of chest wall or PL 3 tumors is advised. CONCLUSIONS: The T subcommittee members proposed not to implement any changes and keep the current eighth-edition T descriptors for the ninth edition.

Myocardial Strain Derived from 13N-ammonia Positron Emission Tomography: Detection of Ischemia-Related Wall Motion Abnormality.

Background: Due to the limitation of spatial resolution, cardiac nuclear medicine images have not been applied to feature-tracking method to automatic extraction of myocardial contours. We have successfully applied the feature-tracking method to high-resolution cine 13N-ammonia positron emission tomography (PET) images to calculate the regional myocardial strains. Here, we investigate the potential of 13N-ammonia PET-derived strain to detect ischemia-related wall motion abnormality. Methods: Data of adenosine-stress/rest 13N-ammonia PET for 95 coronary artery disease patients was retrospectively analyzed. Using an original algorithm dedicated to 13N-ammonia PET, the longitudinal strain (LS) corresponding to the three main coronary artery territories [right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex coronary artery (LCX)] was calculated from semi-automatic endocardial contours extraction on cine 13N-ammonia PET images of the left ventricular long-axis. The presence of ischemia in three main territories was determined from rest and stress-perfusion images. Results: In all three coronary territories, LS at stress was significantly smaller at rest in the ischemic region RCA: -19.2±8.0% vs. -22.7±6.1%, LAD: -19.0±6.9% vs. -24.4±6.4%, LCX: -20.5%±7.6% vs. -22.6±6.9%). In contrast, in the non-ischemic region, there was no significant difference between the LS at stress and at rest. Receiver-operating-characteristic analysis revealed that using the optimal cutoff of the LS ratio of stress to rest, ischemia could be diagnosed with area under the curve of 0.82 in the RCA, 0.86 in the LAD, and 0.69 in the LCX. Conclusions: Myocardial strain derived from endocardial feature-tracking of 13N-ammonia PET cine imaging is reduced in the ischemia induced by adenosine-stress. The LS ratio of stress to rest may detect wall motion abnormality related to ischemia.

Treatment with trastuzumab deruxtecan in patients with HER2-positive breast cancer and brain metastases and/or leptomeningeal disease (ROSET-BM).

Therapeutic options for breast cancer patients with brain metastases (BM)/leptomeningeal carcinomatosis (LMC) are limited. Here, we report on the effectiveness and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2-positive breast cancer patients with BM. Data were analyzed for 104 patients administered T-DXd. Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), intracranial (IC)-ORR, and IC-PFS were evaluated. ORR by investigator assessment was 55.7% (total population). Median PFS was 16.1 months; 12-month OS rate was 74.9% (total population). Median time-to-treatment failure was 9.7 months. In 51 patients with BM imaging, IC-ORR and median IC-PFS by independent central review were 62.7% and 16.1 months, respectively. In 19 LMC patients, 12-month PFS and OS rates were 60.7% and 87.1%, respectively. T-DXd showed effectiveness regarding IC-ORR, IC-PFS, PFS, and OS in breast cancer patients with BM/active BM, and sustained systemic and central nervous system disease control in LMC patients.Trial Registration: UMIN000044995.

A randomized controlled phase III trial protocol: perioperative pirfenidone therapy in patients with non-small cell lung cancer combined with idiopathic pulmonary fibrosis to confirm the preventative effect against postoperative acute exacerbation: the PIII-PEOPLE study (NEJ034).

Background: Radical treatment for non-small cell lung cancer (NSCLC) combined with idiopathic pulmonary fibrosis (IPF) is challenging to plan due to the invasiveness of lung cancer and an acute exacerbation (AE) of IPF that is sometimes lethal. Methods: We intend to conduct the PIII-PEOPLE study (NEJ034), which is a phase III multicenter prospective randomized controlled clinical trial, to validate the effect of perioperative pirfenidone therapy (PPT), involving oral pirfenidone (600 mg) administration for 14 days after registration followed by oral pirfenidone (1,200 mg) for more than 14 days before surgery, with additional oral pirfenidone resumed and continued after surgery. Another group (control) will be allowed to perform any AE preventative treatment, excluding anti-fibrotic agents. Surgery without any preventative measures is also allowed in the control group. The primary endpoint is the IPF exacerbation rate within 30 days postoperatively. The data analysis will be performed in 2023-2024. Discussion: This trial will validate the perioperative AE suppression effect of PPT, and survival benefits including overall, cancer-free, and IP progression free survival due to PPT. It leads to the establishment of an optimized therapeutic strategy for NSCLC combined with IPF. Trial Registration: This trial has been registered at the UMIN Clinical Trials Registry as UMIN000029411 (http://www.umin.ac.jp/ctr/).

Cardiac magnetic resonance imaging T1 mapping and late gadolinium enhancement entropy: Prognostic value in patients with systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) affects the myocardium, thereby resulting in a poor prognosis. Late gadolinium enhancement (LGE) entropy, derived from routine cardiac magnetic resonance (CMR) LGE images, is an index that reflects the complexity of the left ventricular myocardium. The aim of this study was to investigate whether LGE entropy can serve as a prognostic factor in patients with SSc. METHODS: Twenty-four patients with SSc, who underwent CMR-T1 mapping and LGE to identify myocardial damage, were enrolled, and LGE entropy was measured. Extracellular volume (ECV) values were calculated using the same CMR-LGE images. The endpoint was major adverse cardiac events (MACEs), comprising all-cause death, hospitalization due to heart failure, and the onset of sustained ventricular tachycardia and ventricular fibrillation. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of LGE entropy was analyzed using Kaplan-Meier analysis. RESULTS: The ROC curve analysis demonstrated a cut-off value of 7.39 for MACE with LGE entropy and had a sensitivity and specificity of 80 % and 79 %, respectively. Patients with LGE entropy ≥7.39 had a significantly higher MACE rate than those with LGE entropy <7.39 (p = 0.010). Moreover, LGE entropy ≥7.39 was a poor prognostic factor in patients without elevated ECV values. CONCLUSIONS: LGE entropy can be used to predict MACE and allows for further risk stratification in addition to ECV determination.

Linking cardiac and extracardiac sarcoidosis and their clinical outcome: 18F-FDG PET/CT analysis in patients with systemic cardiac sarcoidosis.

OBJECTIVE: To clarify the link between cardiac sarcoidosis (CS) and extra-CS (ECS) in systemic CS (SCS) patients in terms of extent and clinical outcome by serial FDG-PET/CT. METHODS: Thirty-five SCS patients treated for > 2 years were enrolled in this study. In the overall analysis, patient-based comparisons of the complete resolution (CR) and recurrence rate between CS and ECS lesions were performed. Then, subgroup analyses were performed according to the extent (mono- vs. multi-organ ECS group) and clinical outcome (stable vs. unstable ECS group) of ECS. Pre-treatment cardiac FDG uptake was compared between the mono- and multi-organ ECS groups. The rates of CR, recurrence, and major adverse cardiac events (MACE) were compared between the two groups. RESULTS: The CR rate was significantly higher in CS than ECS lesions [77.1% (27/35) vs. 48.5% (17/35), p = 0.01], whereas recurrence rates were similar between CS and ECS [40.7% (11/27) vs. 58.8% (10/17)]. Both the mono- and multi-organ ECS groups showed similar SUVmax, cardiac metabolic volume, and cardiac metabolic activity in the pre-treatment condition. The CR rates were similar between the mono- and multi-organ ECS groups [71.4% (15/21) vs. 85.7% (12/14)], but the recurrence rate was significantly lower in the multi-organ ECS group [60.0% (9/15) vs. 16.7% (2/12), p = 0.02]. The CR [71.4% (5/7) vs. 78.6% (22/28)] and recurrence rates [60.0% (3/5) vs. 36.3% (8/22)] were not significantly different between the stable and unstable ECS groups. The occurrence of MACE was also not significantly different between the mono- and multi-organ ECS groups [19.0% (4/21) vs. 28.6% (4/14)] or between the stable and unstable ECS groups [42.9% (3/7) vs. 17.8% (5/28)]. CONCLUSIONS: CS lesions respond to treatment better than ECS lesions, and the extent and clinical outcome of ECS lesion are not linked with those of CS lesions.

Out-of-Plane Needle Placements Using 3D Augmented Reality Protractor on Smartphone: An Experimental Phantom Study.

PURPOSE: To evaluate the accuracy of needle placement using a three-dimensional (3D) augmented reality (AR) protractor on smartphones (AR Puncture). MATERIALS AND METHODS: An AR protractor that can be rotated in three directions against the CT plane with angle guidance lines for smartphones was developed. The protractor center can be adjusted to an entry point by manually moving the smartphone with the protractor center fixed at the center of the screen (Fix-On-Screen) or by image tracking with a printed QR code placed at an entry point (QR-Tracking). Needle placement was performed by viewing a target line in the tangent direction with the Bull's eye method. The needle placement errors placed by four operators in six out-of-plane directions in a phantom using a smartphone (iPhone XR, Apple, Cupertino, CA, USA) were compared with two registration methods. RESULTS: No significant difference in the average needle placement error was observed between the Fix-On-Screen and QR-Tracking methods (5.6 ± 1.7 mm vs. 6.1 ± 2.9 mm, p = 0.475). The average procedural time of the Fix-On-Screen method was shorter than that of the QR-Tracking method (71.0 ± 23.9 s vs. 98.4 ± 59.5 s, p = 0.042). CONCLUSION: The accuracies of out-of-plane needle placements using the 3D AR protractor with the two registration methods were equally high, with short procedure times. In clinical use, the Fix-On-Screen registration method would be more convenient because no additional markers are required.

Prediction of cardiovascular events using myocardial strain ratio derived from 13N-ammonia positron emission tomography.

OBJECTIVES: Myocardial flow reserve (MFR), derived from ammonia N-13 positron emission tomography (NH3-PET), can predict the prognosis of patients with various heart diseases. We aimed to investigate whether myocardial strain ratio (MSR) was useful in predicting MACE and allowed for further risk stratification of cardiovascular events in patients with ischemic heart disease (IHD) in addition to MFR. METHODS: Ninety-five patients underwent NH3-PET because of IHD. MFR was determined as the ratio of hyperemic to resting myocardial blood flow (MBF). MSR was defined as the ratio of strains at stress and rest. The endpoint was major adverse cardiac events (MACE), including all-cause death, acute coronary syndrome, heart failure hospitalization, and revascularization. The ability to predict MACE was assessed using receiver operating characteristic (ROC) analysis, and the predictability of ME was analyzed using Kaplan-Meier analysis. The Cox proportional hazards regression model was used to calculate the hazard ratio (HR) with 95% confidence interval (CI). RESULTS: The ROC curve analysis demonstrated a cutoff of 0.93 for MACE with MSR (sensitivity and specificity of 77% and 71%, respectively). Patients with MSR < 0.93 displayed a significantly higher MACE rate than those with MSR ≥ 0.93 (p = 0.0036). The Cox proportional hazards regression analysis indicated that MSR was an independent marker that could predict MACE in imaging and clinical parameters (HR, 7.32; 95% CI: 1.59-33.7, p = 0.011). CONCLUSIONS: MSR was an independent predictor of MACE and was useful for further risk stratification in IHD. MSR has the potential for a new indicator of revascularization in patients with IHD. KEY POINTS: • We hypothesized that combining myocardial flow reserve (MFR) with the myocardial strain ratio (MSR) obtained by applying the feature-tracking technique to ammonia N-13 PET would make it predictive of major adverse cardiac events (MACE) compared to MFR alone. • MSR was an independent predictor of MACE, allowing for further risk stratification in addition to MFR in patients with ischemic heart disease. • MSR is a potential new indicator of revascularization.

FDG uptake patterns in isolated and systemic cardiac sarcoidosis.

AIMS: We aimed to investigate the pre-treatment characteristics and treatment responses of isolated and systemic cardiac sarcoidosis (ICS and SCS) from FDG-PET/CT studies and to compare the prognoses of the two groups. METHODS: FDG-PET/CT images taken before and after treatment of 31 ICS and 91 SCS patients were analyzed retrospectively. Treatment response and recurrence were determined from the course of FDG-PET/CT. Treatment response and the incidence of both recurrence and major adverse cardiac events (MACE) were assessed in 16 ICS and 35 SCS patients who had been treated for more than 2 years. RESULTS: A focal uptake pattern was more often observed than a focal-on-diffuse uptake pattern in both the ICS (74.2%) and SCS (63.7%) groups. Right ventricular involvement was significantly more frequent in SCS than ICS (44.0% vs. 9.6%, p < .001). SUVmax, cardiac metabolic volume (CMV), and cardiac metabolic activity (CMA) were significantly higher in SCS than ICS (SUVmax, 9.1 ± 4.1 vs. 4.8 ± 2.1; CMV, 118.0 ± 111.3 ml vs. 68.3 ± 94.7 ml; CMA, 541.6 ± 578.7 MBq vs. 265.1 ± 396.0 MBq, p < .001). Treatment responses in the two groups were similar, and complete resolution of cardiac uptake after immunosuppressive treatment was obtained in 62.5% of ICS patients and 77.1% of SCS patients (not significantly different). Likewise, no significant difference was found in the incidence of recurrence (40.0% for ICS, 44.4% for SCS) or MACE (25.0% for ICS, 22.8% for SCS). CONCLUSION: SCS patients had more active and extensive CS lesions than ICS patients before treatment, but the two groups showed similar treatment responses and prognoses.

Adverse Cardiac Events in Cardiac Sarcoidosis Prediction by 123I-betamethyl-p-iodophenyl-pentadecanoic Acid Single-Photon Emission Computed Tomography and Cardiac Magnetic Resonance Late Gadolinium Enhancement.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging can help detect myocardial damage. 123I-betamethyl-p-iodophenyl-pentadecanoic acid single-photon emission computed tomography (BMIPP-SPECT) was developed to evaluate fatty acid metabolism and has been reported to help detect myocardial damage in cardiac sarcoidosis (CS). We analyzed data from CMR-LGE and performed BMIPP-SPECT in patients with CS taking prednisolone and investigated the association of BMIPP-SPECT with LGE as a prognostic factor in CS. Patients with CS who underwent BMIPP-SPECT and CMR-LGE at the time of diagnosis within 2 months were classified into those with and without a major adverse cardiac event (MACE). Total BMIPP-SPECT defect score (BDS) and LGE extent score (LES) were used to estimate myocardial damage. The relation between BDS and LES was explored using Pearson's correlation coefficient. Their ability to predict MACEs was analyzed using Kaplan-Meier analysis. Medical data of 45 patients were analyzed retrospectively (mean follow-up, 4.5 years). BDS and LES were significantly correlated (p <0.0001). BDS was significantly greater for the group with MACE than that without MACE (p = 0.0008). LES of patients with MACE was significantly greater than those without MACE (p = 0.0045). Patients with BDS ≥16 had a significantly higher MACE rate than those with BDS <16 (p = 0.0029). The group with LES ≥9 was significantly associated with MACE (p = 0.0098). In conclusion, BDS reflected myocardial damage similar to that detected by CMR-LGE and was a predictive marker of MACE in patients with CS. BMIPP-SPECT may help predict the prognosis of patients with CS who cannot undergo CMR-LGE.

Dynamic coronary CT Angiography-Estimated coronary flow in Non-Obstructive, Plaque-free coronary Arteries: Association with dyslipidemia and diabetes.

Rationale and Objectives: In this study, we implemented dynamic coronary CT angiography (CCTA) in order to estimate the coronary flow rate in morphologically normal coronary arteries as well as to identify factors affecting the coronary flow rate. Materials and Methods: We retrospectively enrolled 95 consecutively presenting patients without stenosis or plaque in their major coronary arteries on CCTA conducted with a 320-detector scanner (mean age, 57 years; 43 % men). Time-attenuation curves of the distal sites of the major coronary arteries and the aortic root were extracted from dynamic CCTA data. Coronary flow rate, an indicator of coronary blood flow, was calculated via a convolution-integration method integrating the two curves. Patients with dyslipidemia were divided according to the presence or absence of familial hypercholesterolemia (FH) as well as according to the receipt of statin therapy. Results: We found that the coronary flow rate was statistically significantly lower in statin-naïve patients with dyslipidemia (n = 27, 0.56 ± 0.10) than in patients without dyslipidemia (n = 32, 0.64 ± 0.10, p = 0.0013). In FH (n = 26), the coronary flow rate was statistically significantly lower in statin-naïve patients (n = 7, 0.65 ± 0.08) than in those taking statins (n = 19, 0.72 ± 0.10, p = 0.0221). Coronary flow rate likewise exhibited a statistically significant negative correlation with hemoglobin A1c (Pearson r, -0.437; p = 0.0003), but no correlation with other coronary risk factors. The coronary flow rate was statistically significantly lower in patients with diabetes (n = 14, 0.55 ± 0.10) than in those without diabetes (n = 81, 0.61 ± 0.11, p = 0.0461). Conclusion: We found a reduction in coronary flow rate in patients with statin-naive dyslipidemia and diabetes, even within morphologically normal coronary arteries.

A case of lung intravascular large B cell lymphoma developed with respiratory failure rescued by corticosteroid prior to definite diagnosis.

A 56-year-old man complained progressive dyspnea, fatigue and fever for one month. His chest CT exhibited faint ground-glass opacities, and the levels of serum LDH and soluble interleukin 2 receptor were markedly elevated. Positron emission tomography (PET) showed high uptake of 18-fluoro deoxy glucose (18FDG) only on both lungs. We performed transbronchial lung biopsies (TBLB) for the diagnosis. After bronchoscopy, he had prolonged hypoxemia. Because defects of 99m-Technetium macroaggregated albumin (99mTc-MAA) in pulmonary blood flow scintigraphy were consistent with the distribution of 18FDG uptake in PET, we speculated that the presence of intravascular lymphoma (IVL) cells in the capillaries might have behaved like tumor embolism. We started rescue by prednisolone based on treatment of lymphoma. As a result, his hypoxemia was gradually improved. Histological findings in TBLB specimen showed that CD20+CD79+Bcl-2+c-myc+ lymphoma cells were localized to small vessel lumina in alveoli and bronchioles, and he was definitely diagnosed with lung intravascular large B cell lymphoma (IVLBCL). He was treated with complete cyclophosphamide, doxorubicin, vincristine, and prednisolone with rituximab (R-CHOP) in combination with intrathecal methotrexate injection. After eight cycles of R-CHOP and three times of intrathecal methotrexate, 18FDG uptake of PET on both lungs completely disappeared, achieving complete metabolic remission. We experienced a rare case of lung IVLBCL developed with respiratory failure successfully rescued by prednisolone prior to definite diagnosis.

First Validation of Myocardial Flow Reserve Derived from Dynamic 99mTc-Sestamibi CZT-SPECT Camera Compared with 13N-Ammonia PET.

13N-ammonia positron emission tomography (NH3-PET) can evaluate myocardial blood flow (MBF) at rest, stress, and myocardial flow reserve (MFR) as well as the ratio of MBF at stress to that at rest. MFR is useful in predicting the prognoses of patients with various heart diseases. Cadmium-zinc-telluride single photon emission computed tomography (CZT-SPECT) enables us to acquire dynamic images of radiotracer kinetics and measure original MBF and MFR using 99mTc-sestamibi. This study aimed to investigate the utility of CZT-SPECT for quantitative assessment of MBF compared to NH3-PET. We validated the correlation of MBF and MFR between CZT-SPECT and NH3-PET. Fourteen patients using one-day rest/stress CZT-SPECT, D-SPECT followed by NH3-PET within 1 month were enrolled and analyzed prospectively. The reproducibility of the MBF and MFR obtained with these two methods was examined using Spearman's correlation coefficient and Bland-Altman plot analysis. The diagnostic value of D-SPECT for abnormal MFR defined using NH3-PET results as MFR < 2.0 was assessed using receiver-operating characteristic (ROC) analysis. The median duration between D-SPECT and NH3-PET was 20 days. Although MBF was overestimated by D-SPECT compared to NH3-PET at high value (mean difference, 0.43 [0.34-0.53]), MBF and MFR were correlated with the two modalities (MBF: r = 0.71, P < 0.0001, MFR: r = 0.60, P < 0.0001). The ROC curve analysis demonstrated a cutoff of 1.6 for detecting abnormal MFR with D-SPECT (sensitivity, 68%; specificity, 91%; AUC, 0.75). MBF and MFR obtained using D-SPECT and NH3-PET had a good correlation, suggesting that the quantitative MFR evaluation by CZT-SPECT may help understand the trend of NH3-PET MFR.