Feasibility, Repeatability, and Correlation to Lung Function of Phase-Resolved Functional Lung (PREFUL) MRI-derived Pulmonary Artery Pulse Wave Velocity Measurements.

BACKGROUND: Pulse wave velocity (PWV) in the pulmonary arteries (PA) is a marker of vascular stiffening. Currently, only phase-contrast (PC) MRI-based options exist to measure PA-PWV. PURPOSE: To test feasibility, repeatability, and correlation to clinical data of Phase-Resolved Functional Lung (PREFUL) MRI-based calculation of PA-PWV. STUDY TYPE: Retrospective. SUBJECTS: 79 (26 female) healthy subjects (age range 19-78), 58 (24 female) patients with chronic obstructive pulmonary disease (COPD, age range 40-77), 60 (33 female) patients with suspected pulmonary hypertension (PH, age range 28-85). SEQUENCE: 2D spoiled gradient echo, 1.5T. ASSESSMENT: PA-PWV was measured from PREFUL-derived cardiac cycles based on the determination of temporal and spatial distance between lung vasculature voxels using a simplified (sPWV) method and a more comprehensive (cPWV) method including more elaborate distance calculation. For 135 individuals, PC MRI-based PWV (PWV-QA) was measured. STATISTICAL TESTS: Intraclass-correlation-coefficient (ICC) and coefficient of variation (CoV) were used to test repeatability. Nonparametric tests were used to compare cohorts. Correlation of sPWV/cPWV, PWV-QA, forced expiratory volume in 1 sec (FEV1 ) %predicted, residual volume (RV) %predicted, age, and right heart catheterization (RHC) data were tested. Significance level α = 0.05 was used. RESULTS: sPWV and cPWV showed no significant differences between repeated measurements (P-range 0.10-0.92). CoV was generally lower than 15%. COPD and PH patients had significantly higher sPWV and cPWV than healthy subjects. Significant correlation was found between sPWV or cPWV and FEV1 %pred. (R = -0.36 and R = -0.44), but not with RHC (P-range -0.11 - 0.91) or age (P-range 0.23-0.89). Correlation to RV%pred. was significant for cPWV (R = 0.42) but not for sPWV (R = 0.34, P = 0.055). For all cohorts, sPWV and cPWV were significantly correlated with PWV-QA (R = -0.41 and R = 0.48). DATA CONCLUSION: PREFUL-derived PWV is feasible and repeatable. PWV is increased in COPD and PH patients and correlates to airway obstruction and hyperinflation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Chronic Thromboembolic Pulmonary Hypertension Perioperative Monitoring Using Phase-Resolved Functional Lung (PREFUL)-MRI.

BACKGROUND: The translation of phase-resolved functional lung (PREFUL)-MRI to routine practice in monitoring chronic thromboembolic pulmonary hypertension (CTEPH) still requires clinical corresponding imaging biomarkers of pulmonary vascular disease. PURPOSE: To evaluate successful pulmonary endarterectomy (PEA) via PREFUL-MRI with pulmonary pulse wave transit time (pPTT). STUDY TYPE: Retrospective. POPULATION: Thirty CTEPH patients and 12 healthy controls were included. FIELD STRENGTH/SEQUENCE: For PREFUL-MRI a 2D spoiled gradient echo sequence and for DCE-MRI a 3D time-resolved angiography with stochastic trajectories (TWIST) sequence were performed on 1.5T. ASSESSMENT: Eight coronal slices of PREFUL-MRI were obtained on consecutive 13 days before and 14 days after PEA. PREFUL quantitative lung perfusion (PREFULQ ) phases over the whole cardiac cycle were calculated to quantify pPTT, the time the pulmonary pulse wave travels from the central pulmonary arteries to the pulmonary capillaries. Also, perfusion defect percentage based on pPTT (QDPpPTT ), PREFULQ (QDPPREFUL ), and V/Q match were calculated. For DCE-MRI, pulmonary blood flow (PBF) and QDPPBF were computed as reference. For clinical correlation, mean pulmonary arterial pressure (mPAP) and 6-minute walking distance were evaluated preoperatively and after PEA. STATISTICAL TESTS: The Shapiro-Wilk test, paired two-sided Wilcoxon rank sum test, Dice coefficient, and Spearman's correlation coefficient (ρ) were applied. RESULTS: Median pPTT was significantly lower post PEA (139 msec) compared to pre PEA (193 msec), P = 0.0002. Median pPTT correlated significantly with the mPAP post PEA (r = 0.52, P < 0.008). Median pPTT was distributed more homogeneously after PEA: IQR pPTT decreased from 336 to 281 msec (P < 0.004). Median PREFULQ (P < 0.0002), QDPpPTT (P < 0.0478), QDPPREFUL (P < 0.0001) and V/Q match (P < 0.0001) improved significantly after PEA. Percentage change of PREFULQ correlated significantly with percentage change of 6-minute walking distance (ρ = 0.61; P = 0.0031) 5 months post PEA. DATA CONCLUSION: Perioperative perfusion changes in CTEPH can be detected and quantified by PREFUL-MRI. Normalization of pPTT reflects surgical success and improvement of PREFULQ predicts 6-minute walking distance changes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 2 J. Magn. Reson. Imaging 2020;52:610-619.

Effect of Indacaterol/Glycopyrronium on Pulmonary Perfusion and Ventilation in Hyperinflated Patients with Chronic Obstructive Pulmonary Disease (CLAIM). A Double-Blind, Randomized, Crossover Trial.

Rationale: In the CLAIM study, dual bronchodilation with indacaterol/glycopyrronium (IND/GLY) significantly reduced hyperinflation, which translated into improved cardiac function, measured by left ventricular end-diastolic volume and cardiac output. Pulmonary microvascular blood flow (PMBF) is reduced in chronic obstructive pulmonary disease (COPD); however, the effect of reduced lung hyperinflation on PMBF remains unknown. Objectives: To determine the effect of lung deflation with IND/GLY on PMBF and regional pulmonary ventilation using magnetic resonance imaging (MRI) in hyperinflated patients with COPD. Methods: In this double-blind, randomized, two-period crossover study, gadolinium-enhanced MRI and phase-resolved functional lung MRI were used to measure PMBF and regional ventilation, respectively, in patients with COPD receiving IND/GLY versus placebo. Measurements and Main Results: Sixty-two patients were randomized to receive once-daily IND/GLY (110/50 µg) for 14 days, followed by 14 days of placebo, or vice versa. Treatment periods were separated by a 14-day washout. Sixty patients were included in the per-protocol analysis. MRI measurements showed significant improvements in total PMBF (P = 0.006) and regional PMBF (P values for individual lobes were between 0.004 and 0.022) in response to IND/GLY versus placebo. Regional ventilation was also significantly improved with IND/GLY, as evidenced by a 12.4% increase versus placebo (P = 0.011), a 14.3% relative decrease in ventilation defect percentage of nonventilated/hypoventilated lung tissue (cutoff was defined as 0.075 regional ventilation; P = 0.0002), and a 15.7% reduction in the coefficient of variation of regional ventilation compared with placebo (P < 0.0001). Conclusions: Pharmacologic intervention with IND/GLY improves pulmonary microvascular blood flow and regional ventilation in patients with COPD with hyperinflation. Clinical trial registered with www.clinicaltrials.gov (NCT02442206).

Regional investigation of lung function and microstructure parameters by localized 129 Xe chemical shift saturation recovery and dissolved-phase imaging: A reproducibility study.

PURPOSE: To evaluate the reproducibility and regional variation of parameters obtained from localized 129 Xe chemical shift saturation recovery (CSSR) MR spectroscopy in healthy volunteers and patients with chronic obstructive pulmonary disease (COPD) and to compare the results to 129 Xe dissolved-phase MR imaging. METHODS: Thirteen healthy volunteers and 10 COPD patients were scanned twice using 129 Xe dissolved-phase imaging, CSSR, and ventilation imaging sequences. A 16-channel phased-array coil in combination with the regularized spectral localization achieved by sensitivity heterogeneity (SPLASH) method was used to perform a regional analysis of CSSR data. Lung function and microstructural parameters were obtained using Patz model functions and their reproducibility was assessed. RESULTS: The Patz model alveolar wall thickness parameter shows good reproducibility on a regional basis with a median coefficient of variation of 6.5% in healthy volunteers and 12.4% in COPD patients. Significant regional differences of lung function parameters derived from localized CSSR were found in healthy volunteers and correlations with spirometric indices were found. CONCLUSION: Localized 129 Xe CSSR provides reproducible estimates of alveolar wall thickness and is able to detect regional differences of lung microstructure.

Cardio-pulmonary MRI for detection of treatment response after a single BPA treatment session in CTEPH patients.

OBJECTIVES: Chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with balloon pulmonary angioplasty (BPA) in inoperable patients. Sensitive non-invasive imaging methods are missing to detect treatment response after a single BPA treatment session. Therefore, the aim of this study was to measure treatment response after a single BPA session using cardio-pulmonary MRI. MATERIALS AND METHODS: Overall, 29 patients with CTEPH were examined with cardio-pulmonary MRI before and 62 days after their initial BPA session. Pulmonary blood flow (PBF), first-pass bolus kinetic parameters, and biventricular mass and function were determined. Multiple linear regression analysis was implemented to estimate the relationship of PBF change in the treated lobe with treatment change of full width at half maximum (FWHM), cardiac output (CO), ventricular mass index (VMI), pulmonary transit time (PTT) and PBF change in the non-treated lobes. Paired Wilcoxon rank sum test and Spearman rho correlation were used. RESULTS: After BPA regional PBF increased in the treated lobe (p < 0.0001) as well as in non-treated lobes (p = 0.015). PBF treatment changes in the treated lobe were significantly larger compared with the non-treated lobes (p = 0.0049). Change in NT proBNP, MRI-derived mean pulmonary artery pressure (mPAP), PTT, FWHM, right ventricular (RV) ejection fraction, RV stroke volume, CO, VMI and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05). PBF changes in the treated lobe were independently predicted by PTT as well as PBF change in the non-treated lobes. CONCLUSION: Cardio-pulmonary MRI detects and quantifies treatment response after a single BPA treatment session. KEY POINTS: • Two months after BPA regional parenchymal pulmonary perfusion (PBF) increased in the total lung parenchyma (p = 0.005), the treated lobes (p < 0.0001) and non-treated lobes (p = 0.015). • The PBF treatment changes in the treated lobe were significantly larger than in the non-treated lobes (p = 0.0049). • Change in NT proBNP, MRI-derived mean pulmonary artery pressure, pulmonary transit time, full width at half maximum, right ventricular (RV) ejection fraction, RV stroke volume, cardiac output, ventricular mass index and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05).

Breath-hold and free-breathing 2D phase-contrast MRI for quantification of oxygen-induced changes of pulmonary circulation dynamics in healthy volunteers.

PURPOSE: To evaluate the effect of inhaled 100% oxygen on pulmonary circulation dynamics in healthy volunteers using 2D phase-contrast magnetic resonance imaging (2D PC MRI). MATERIALS AND METHODS: Twenty-one healthy volunteers were examined at 1.5T. Through-plane 2D PC MRI measurements were performed in the main pulmonary artery during free-breathing and breath-hold. Acceleration time and volume, maximum and minimum area, area change, average and maximum mean velocity, forward volume, heart rate, as well as blood pressure were determined. At baseline, subjects breathed room air. After application of a closed-fit full face mask, three further measurements were conducted: at room air (control), directly after starting 15 L/min 100% oxygen (wash-in), and after 5 minutes during continuous oxygen supply (saturation). Data were analyzed with a mixed linear model. Skewed distributed variables were rank-transformed. Tukey contrasts with family-wise adjusted P-values were applied for pairwise comparisons. RESULTS: Inhaled oxygen affected several hemodynamic parameters. Average mean velocity (P < 0.01: breath-hold during wash-in and saturation, P = 0.03: free-breathing during saturation) and maximum mean velocity (P < 0.01: breath-hold and free-breathing during saturation) decreased. When obtained during free-breathing, acceleration volume (P = 0.02: saturation), area change (P = 0.02: saturation), and maximum area (P = 0.02: wash-in, P = 0.03: saturation) increased, while minimum area and forward volume did not change. CONCLUSION: Oxygen alters pulmonary circulation dynamics in the main pulmonary artery of healthy volunteers, which can be reliably detected using 2D phase-contrast MRI. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1698-1706.

Histamine induces chemotaxis and phagocytosis in murine bone marrow-derived macrophages and RAW 264.7 macrophage-like cells via histamine H4-receptor.

OBJECTIVE: Expression and function of histamine H4-receptor, an immunomodulatory receptor involved in inflammatory diseases, on murine macrophages, which are vital for immunity, were investigated. MATERIALS AND METHODS: The expression pattern of histamine receptors on bone marrow-derived macrophages of BALB/c mice and on RAW 264.7 cells was studied at the mRNA level by reverse transcription polymerase chain reaction. The functional relevance of histamine receptors was investigated by analyzing histamine-induced chemotaxis and phagocytosis in the presence of histamine receptor antagonists mepyramine (histamine H1-receptor), famotidine (histamine H2-receptor), thioperamide (histamine H3/4-receptors) and JNJ7777120 (histamine H4-receptor). RESULTS: Both bone marrow-derived macrophages and RAW 264.7 cells express mRNA for histamine H1-receptor and histamine H4-receptor. Residual amounts of histamine H2-receptor mRNA are found in bone marrow-derived macrophages only. In both cellular models, histamine induced chemotaxis and phagocytic activity, which was reduced by thioperamide as well as by JNJ 7777120, but not by mepyramine or famotidine. CONCLUSION: In murine bone marrow-derived macrophages and RAW 264.7 macrophage-like cells histamine H4-receptor mediates chemotaxis and phagocytic activity.

Feasibility of Using a Novel Drop-In Gamma Probe for 99mTc-PSMA-I&S-Guided Lymph Node Detection During Robot-Assisted Radical Prostatectomy for Primary Prostate Cancer.

PURPOSE: Prostate-specific membrane antigen (PSMA)-targeted radioguided surgery (RGS) has gained increased interest in prostate cancer (PCa). This analysis aims to evaluate the feasibility, safety, and limitations of RGS with a novel drop-in gamma probe in primary PCa. PATIENTS AND METHODS: The data of 13 patients with primary PCa undergoing RGS were analyzed retrospectively. After preoperative administration of 99mTc-PSMA-I&S, a SPECT/CT was conducted and a robotic radical prostatectomy was performed the following day including intraoperative assessment of the lymph node stations using a novel robotic drop-in gamma probe. This was followed by an extended pelvic lymph node dissection (ePLND) with ex vivo control measurement using the drop-in and a conventional rigid gamma probe. RESULTS: Eleven patients (median PSA value of 11 ng/mL) had high-risk and 2 patients had intermediate-risk PCa. Overall, a median of 22 ePLND lymph nodes were dissected. In 1 patient, preoperative SPECT/CT imaging showed suspicious lymph nodes, which could be confirmed intraoperatively with the robotic drop-in probe and subsequently in the final histopathological analysis. RGS failed to identify 2 patients with micrometastases (<3 mm) preoperatively and intraoperatively. No postoperative complications related to 99mTc-PSMA-I&S RGS or ePLND occurred. CONCLUSIONS: RGS with the novel drop-in gamma probe and 99mTc-PSMA-I&S allows for a reliable intraoperative screening for lymph node metastases in robot-assisted radical prostatectomy for primary PCa with an acceptable safety profile. However, limitations in the detection of micrometastases need to be overcome before omitting extended ePLND in patients at risk for lymphatic spread.

[Positron emission tomography in oncology]. / Positronenemissionstomographie in der Onkologie.

Positron emission tomography (PET) is a highly sensitive imaging tool that noninvasively characterizes metabolic processes and molecular targets. PET has become an integral part of oncological diagnostics and an increasingly important tool for oncological therapy management. PET assessment, for example, directly influences treatment escalation or de-escalation in context of Hodgkin lymphomas or is, in case of lung cancer, able to reduce unnecessary surgeries. Hence, molecular PET imaging represents an indispensable tool in the development of personalized treatments. Furthermore, the development of new radiotracers for specific cell surface structures offers a promising potential for diagnostics and-combined with therapeutic nuclides-also for therapies. One recent example are radioligands targeting prostate-specific membrane antigen, which are relevant in prostate cancer.

[Hereditary kidney cancer - easily clarified and diagnosed with ToSCaNA]. / Hereditäre Nierentumore ­ einfach abgeklärt mit ToSCaNA.

BACKGROUND: In recent years great improvements in the diagnosis and differentiation of hereditary syndroms with predisposition for kidney cancer have been achieved. It has been assumed that 5-8% of all kidney cancer have a hereditary origin. In reality, this number will probably be much higher as many genetic aspects of kidney cancer are still not entirely known. Hereditary kidney cancer usually shows two characteristic properties: While the median age of diagnosis of sporadic renal cell carcinoma is 64 years, patients with a hereditary tumor predisposition are about 20 years younger at the time of diagnosis. Additionally, their tumors often occur multifocal/bilateral. Therefore, a special management with extended diagnostics is necessary for these young kidney cancer patients. In literature many reports on hereditary syndromes with kidney cancer predisposition exist. Though, these papers usually put their focus on single syndromes rather than on the aspects of kidney cancer. The goal of this article is to present the practicing urologist with a compact overview of the most important hereditary syndromes with kidney cancer predisposition and by this improve the primary diagnostic and treatment of renal cancer patients and their relatives. MATERIAL/METHODS: We conducted a literature search on the five most important hereditary syndromes with kidney cancer association and summarized the results in a chart. Additionally, we formed the acronym ToSCaNA combining the most important extrarenal manifestations of the syndromes. Based on this data, a diagnostic workflow and treatment path was established. RESULTS: All in all, hereditary kidney cancer is a rare entity, which nonetheless could present as a significant number in high-volume centers. For doctors who scarcely get in contact with these types of tumors, the acronym and workflow could pose a valuable asset for their clinical diagnostic portfolio. An early identification and diagnostic work-up of affected patients and their relatives is crucial for appropriate treatment and surveillance and allows the identification/treatment of additionally affected relatives. CONCLUSION: In patients with young age of onset and multifocal/bilateral occurrence of kidney cancer, hereditary syndromes should always be considered. The initial suspicion of a hereditary genesis of the cancer can be further evaluated by the acronym ToSCaNA and the presented workflow.

Cardiac Fibroblast Activation in Patients Early After Acute Myocardial Infarction: Integration with MR Tissue Characterization and Subsequent Functional Outcome.

After acute myocardial infarction (AMI), fibroblast activation protein (FAP) upregulation exceeds the infarct region. We sought further insights into the physiologic relevance by correlating FAP-targeted PET with tissue characteristics from cardiac MRI (CMR) and functional outcome. Methods: Thirty-five patients underwent CMR, perfusion SPECT, and 68Ga-FAP inhibitor (FAPI)-46 PET/CT within 11 d after AMI. Infarct size was determined from SPECT by comparison to a reference database. For PET, regional SUVs and isocontour volumes of interest determined the extent of cardiac FAP upregulation (FAP volume). CMR yielded functional parameters, area of injury (late gadolinium enhancement [LGE]) and T1/T2 mapping. Follow-up was available from echocardiography or CMR after 139.5 d (interquartile range, 80.5-188.25 d) (n = 14). Results: The area of FAP upregulation was significantly larger than the SPECT perfusion defect size (58% ± 15% vs. 23% ± 17%, P < 0.001) and infarct area by LGE (28% ± 11%, P < 0.001). FAP volume significantly correlated with CMR parameters at baseline (all P < 0.001): infarct area (r = 0.58), left ventricle (LV) mass (r = 0.69), end-systolic volume (r = 0.62), and end-diastolic volume (r = 0.57). Segmental analysis revealed FAP upregulation in 308 of 496 myocardial segments (62%). Significant LGE was found in only 56% of FAP-positive segments, elevated T1 in 74%, and elevated T2 in 68%. Fourteen percent (44/308) of FAP-positive segments exhibited neither prolonged T1 or T2 nor significant LGE. Of note, FAP volume correlated only weakly with simultaneously measured LV ejection fraction at baseline (r = -0.32, P = 0.07), whereas there was a significant inverse correlation with LV ejection fraction obtained at later follow-up (r = -0.58, P = 0.007). Conclusion: Early after AMI and reperfusion therapy, activation of fibroblasts markedly exceeds the hypoperfused infarct region and involves noninfarcted myocardium. The 68Ga-FAPI PET signal does not match regional myocardial tissue characteristics as defined by CMR but is predictive of the evolution of ventricular dysfunction. FAP-targeted imaging may provide a novel biomarker of LV remodeling that is complementary to existing techniques.

4D-flow cardiac magnetic resonance imaging after aortic root replacement with long-valved decellularized aortic homografts: comparison to valve-sparing aortic root replacement and healthy controls.

OBJECTIVES: Long-valved decellularized aortic homografts (DAH) may be used in young patients to treat aortic valve disease associated with aortic root dilatation, thereby eliminating the need for prosthetic material and anticoagulation. METHODS: Thirty-three male subjects in 3 equally sized cohorts were compared: patients following DAH implantation with a median age of 29 years [interquartile range (IQR) 27.5-37.5], patients post-valve-sparing aortic root replacement (VSARR), median 44 years (IQR 31.5-49) and healthy controls, median 33 years (IQR 28-40, P = 0.228). Time-resolved three-dimensional phase-contrast cardiac magnetic resonance imaging was performed to assess maximum blood flow velocity, pulse wave velocity, mechanical energy loss (EL), wall shear stress and flow patterns (vorticity, eccentricity, helicity) in 5 different planes of the aorta. RESULTS: The mean time between surgery and cardiovascular magnetic resonance was 2.56 ± 2.0 years in DAH vs 2.67 ± 2.1 in VSARR, P = 0.500. No significant differences in maximum velocity and pulse wave velocity were found between healthy controls and DAH across all planes. Velocity in the proximal aorta was significantly higher in VSARR (182.91 ± 53.91 cm/s, P = 0.032) compared with healthy controls. EL was significantly higher in VSARR in the proximal aorta with 1.85 mW (IQR 1.39-2.95) compared with healthy controls, 1.06 mW (0.91-1.22, P = 0.016), as well as in the entire thoracic aorta. In contrast, there was no significant EL in DAH in the proximal, 1.27 m/W (0.92-1.53, P = 0.296), as well as in the thoracic aorta, 7.7 m/W (5.25-9.90, P = 0.114), compared with healthy controls. There were no significant differences in wall shear stress parameters for all 5 regions of the thoracic aorta between the 3 groups. DAH patients, however, showed more vorticity, helicity and eccentricity in the ascending aorta compared with healthy controls (P < 0.019). CONCLUSIONS: Decellularized long aortic homografts exhibit near to normal haemodynamic parameters 2.5 years postoperatively compared with healthy controls and VSARR.

Perioperative CTEPH patient monitoring with 2D phase-contrast MRI reflects clinical, cardiac and pulmonary perfusion changes after pulmonary endarterectomy.

Magnetic resonance imaging (MRI) is an emerging tool for diagnosis and treatment monitoring of chronic thromboembolic pulmonary hypertension (CTEPH). The current study aims to identify central pulmonary arterial hemodynamic parameters that reflect clinical, cardiac and pulmonary changes after PEA. 31 CTEPH patients, who underwent PEA and received pre- and postoperative MRI, were analyzed retrospectively. Central pulmonary arterial blood flow, lung perfusion and right heart function data were derived from MRI. Mean pulmonary arterial pressure (mPAP) and 5-month follow-up six-minute walk-distance (6MWD) were assessed. After PEA, mPAP decreased significantly and patients achieved a higher 6MWD. Central pulmonary arterial blood flow velocities, pulmonary blood flow (PBF) and right ventricular function increased significantly. Two-dimensional (2D) phase-contrast (PC) MRI-derived average mean velocity, maximum mean velocity and deceleration volume changes after PEA correlated with changes of 6MWD and right heart ejection fraction (RVEF). Deceleration volume is a novel 2D PC MRI parameter showing further correlation with PBF changes. In conclusion, 2D PC MRI-derived main pulmonary hemodynamic changes reflect changes of RVEF, PBF and 5-month follow-up 6MWD and may be used for future CTEPH patient monitoring after PEA.