Hematospermia Evaluation at MR Imaging.

Hematospermia is a challenging and anxiety-provoking condition that can manifest as a single episode or recur over the course of weeks to months. It is usually a benign self-limiting condition in younger sexually active males without a history of risk factors such as cancer, urogenital malformations, bleeding disorders, and their associated symptoms. However, patients with recurrent, refractory and painful hematospermia with associated symptoms, such as fever, pain, or weight loss, require evaluation through clinical assessment and noninvasive investigations to rule out underlying pathologic conditions such as ejaculatory obstruction, infectious and inflammatory causes, malignancy, vascular malformations, and systemic disorders that increase the risk of bleeding, especially when presenting in older men. If these investigations are negative, the patient should be reassured and treated accordingly. In the recent past, magnetic resonance (MR) imaging has assumed a major role in the investigation of hematospermia due to its excellent soft-tissue contrast and multiplanar capabilities. In this review, we will discuss the potential causes of hematospermia and its diagnostic workup, including pathophysiology, anatomic considerations, the imaging appearance of associated pathologic conditions, and management. (©)RSNA, 2016.

Primary biliary tract malignancies: MRI spectrum and mimics with histopathological correlation.

Contrast-enhanced magnetic resonance imaging and magnetic resonance cholangiopancreatography (MRCP), due to their excellent soft tissue contrasts, have become first-line noninvasive tests in the characterization and detection of both hepatic and pancreaticobiliary pathologies. MRCP is also helpful in detecting the level and cause of obstruction in patients presenting with jaundice. Cholangiocarcinoma (CCA) is the most common primary malignant tumor arising from the bile duct epithelium, with extrahepatic tumors presenting more often than with intrahepatic ones. However, the diagnosis and management of CCA is made more complex by a variety of malignant and benign conditions that resemble CCA, including hepatocellular carcinoma variants such as the fibrolamellar variant of hepatocellular carcinoma, cholangiocellular carcinoma, biliary metastases, hepatic inflammatory pseudotumor, lymphoepithelioma-like carcinoma, confluent fibrosis, primary sclerosis cholangitis, and the secondary sclerosing cholangitis complex. Consequently, knowledge of the underlying risk factors and imaging characteristics of these conditions is important in differentiating between neoplastic and non-neoplastic conditions in order to reach a definite diagnosis. Endoscopic retrograde cholangiopancreatography should be reserved for those patients who require intervention or biopsy for histopathological diagnosis.

Optimal section thickness for detection of polyps at MR: resolution phantom study.

PURPOSE: To determine (1) the sensitivity for detection of small polyps with varying MR slice thicknesses using a resolution phantom; (2) reader confidence in polyp detection; and (3) image acquisition time. METHODS: A resolution phantom was created using a 3D printer. Polyp morphologies were sessile (height = diameter), flat (height = 1/2 diameter of the base), and pedunculated (stalk length = polyp diameter). Polyp diameters were 5, 7, 10, and 12 mm. Images were acquired with section thicknesses of 5, 3, and 1 mm. Images were independently reviewed by 4 board-certified radiologists who were blinded to phantom design and sequences parameters. Readers recorded maximal polyp diameter and confidence level that a polyp was present on a 1-100 point scale. Image acquisition time was also recorded. RESULTS: All polyps were detected by all 4 readers in the 5-mm-section thickness series. All polyps were detected by 3 readers in the 3- and 1-mm-section thickness series. The fourth reader identified 11/12 polyps in the 3- and 1-mm-section thickness series. Confidence levels were not statistically significantly different for the different section thicknesses (p = 0.28). Increasing the section thickness from 1 to 5 mm decreased image acquisition time from 3 min 54 s to 41 s. CONCLUSIONS: Five-millimeter-section thickness was adequate for identification of 5-12 mm polyps regardless of shape. Pending further reduction in acquisition time, this prototype sequence holds promise for segmental imaging of the colon with MR colonography.

Magnetic resonance imaging of rectal cancer: staging and restaging evaluation.

Magnetic resonance imaging is used to non-invasively stage and restage rectal adenocarcinomas. Accurate staging is important as the depth of tumor extension and the presence or absence of lymph node metastases determines if an individual will undergo preoperative neoadjuvant chemoradiation. Accurate description of tumor location is important for presurgical planning. The relationship of the tumor to the anal sphincter in addition to the depth of local invasion determines the surgical approach used for resection. High-resolution T2-weighted imaging is the primary sequence used for initial staging. The addition of diffusion-weighted imaging improves accuracy in the assessment of treatment response on restaging scans. Approximately 10%-30% of individuals will experience a complete pathologic response following chemoradiation with no residual viable tumor found in the resected specimen at histopathologic assessment. In some centers, individuals with no residual tumor visible on restaging MR who are thought to be at high operative risk are monitored with serial imaging and a "watch and wait" approach in lieu of resection. Normal rectal anatomy, MR technique utilized for staging and restaging scans, and TMN staging are reviewed. An overview of surgical techniques used for resection including newer, minimally invasive endoluminal techniques is included.

Mesenteric masses: approach to differential diagnosis at MRI with histopathologic correlation.

Magnetic resonance imaging (MRI) is an outstanding tool for the identification and characterization of mesenteric masses. Mesenteric masses may be solid or cystic. Most solid mesenteric masses are neoplastic, with sclerosing mesenteritis a notable exception. Entirely cystic mesenteric masses are typically benign. The excellent soft-tissue contrast afforded by MRI aids in narrowing the differential diagnosis of mesenteric masses. Accurately characterizing both solid and cystic mesenteric masses is important, as management ranges from active surveillance to medical management to surgical resection, depending on the tissue composition of the mass. An MRI-based approach to the differential diagnosis of mesenteric masses is presented.

MR imaging of pulmonary embolism: diagnostic accuracy of contrast-enhanced 3D MR pulmonary angiography, contrast-enhanced low-flip angle 3D GRE, and nonenhanced free-induction FISP sequences.

PURPOSE: To evaluate relative detection of pulmonary embolism (PE) with standard bolus-triggered contrast-enhanced breath-hold magnetic resonance (MR) pulmonary angiography, contrast-enhanced recirculation-phase breath-hold low-flip angle three-dimensional (3D) gradient-echo (GRE), and nonenhanced free-induction cardiac- and respiratory-triggered true fast imaging with steady-state precession (FISP) MR sequences. MATERIALS AND METHODS: The study was HIPAA compliant and institutional review board approved. Twenty-two patients with a computed tomographic (CT) angiography diagnosis of PE underwent MR imaging within 48 hours of CT. MR included three complementary techniques: MR pulmonary angiography, 3D GRE, and triggered true FISP. Each sequence was analyzed separately by two independent reviewers who recorded presence of emboli in categorized pulmonary artery anatomic territories. CT angiography results were analyzed by a third independent reviewer, who retrospectively recorded presence of emboli using the same format; these results served as the reference standard. Sensitivity, specificity, and positive and negative predictive values for PE detection were calculated for each MR technique on a per-embolus basis, and 95% confidence intervals were calculated according to the efficient-score method. A two-sample t test was used to compare values among MR techniques. RESULTS: Sensitivities for PE detection were 55% for MR pulmonary angiography, 67% for triggered true FISP, and 73% for 3D GRE MR imaging. Combining all three MR sequences improved overall sensitivity to 84%. Specificity was 100% for all detection methods except for MR pulmonary angiography (one false-positive). Agreement between readers was high (κ = 0.87). Embolus detection rates were lowest in the lingula branch for all MR sequences compared with remainder of the vascular territories (P = .07). CONCLUSION: There are complementary benefits to combining standard MR pulmonary angiography, 3D GRE, and triggered true FISP MR examinations for evaluation of PE.

Hepatocellular carcinoma lesion characterization: single-institution clinical performance review of multiphase gadolinium-enhanced MR imaging--comparison to prior same-center results after MR systems improvements.

PURPOSE: To measure diagnostic performance in the detection of hepatocellular carcinoma (HCC) by using the most recent technology and multiphase gadolinium-enhanced magnetic resonance (MR) imaging and to compare with earlier results at the same institution. MATERIALS AND METHODS: This retrospective study was institutional review board approved and HIPAA compliant. Informed consent was obtained. Between January 2008 and April 2010, 101 patients underwent liver transplantation and pretransplantation abdominal MR imaging within 90 days. Prospective image interpretations from the clinical record were reviewed for documentation of HCC, including size, number, and location. Liver explant histologic examination provided the reference standard for lesion analysis and was performed in axial gross slices in conjunction with the MR imaging report for direct comparison. Tumors were categorized according to size (≥ 2 cm or <2 cm), and MR imaging detection sensitivity, specificity, predictive values, and accuracy were calculated according to category. The Fisher exact test was used to compare results from this study against prior reported results. RESULTS: Thirty-five (34.7%) of 101 patients had HCC at explant analysis. Patient-based analysis of all lesions showed a sensitivity and specificity of 97.1% (34 of 35) and 100% (66 of 66), respectively. For lesions 2 cm or larger, MR imaging had a sensitivity and specificity of 100% (23 of 23) and 100% (78 of 78), respectively. For lesions smaller than 2 cm, MR imaging had a sensitivity and specificity of 82.6% (19 of 23) and 100% (78 of 78), respectively. Lesion-based sensitivity for all tumors was 91.4% (53 of 58) in the current study, compared with 77.8% in 2007 (P = .07). For lesions smaller than 2 cm, the sensitivity was 87.5% (28 of 32) in the current study, compared with 55.6% previously (P = .02). CONCLUSION: MR imaging remains a highly accurate diagnostic method for the preoperative evaluation of HCC, and detection of small (<2 cm) tumors has been significantly improved compared with that of earlier studies.

Optimization of single injection liver arterial phase gadolinium enhanced MRI using bolus track real-time imaging.

PURPOSE: To measure contrast agent enhancement kinetics in the liver and to further evaluate and develop an optimized gadolinium enhanced MRI using a single injection real-time bolus-tracking method for reproducible imaging of the transient arterial-phase. MATERIALS AND METHODS: A total of 18 subjects with hypervascular liver lesions were imaged with four dimensional (4D) perfusion scans to measure time-to-peak (TTP) delays of arterial (aorta-celiac axis), liver parenchyma, liver lesion, portal, and hepatic veins. Time delays were calculated from the TTP-aorta signal, and then related to the gradient echo (GRE) k-space acquisition design, to determine optimized timing for real-time bolus-track triggering methodology. As another measure of significance, 200 clinical patients were imaged with 3D-GRE using either a fixed time-interval or by individualized arterial bolus real-time triggering. Bolus TTP-aorta was calculated and arterial-phase acquisitions were compared for accuracy and reproducibility using specific vascular enhancement indicators. RESULTS: The mean bolus transit-time to peak-lesion contrast was 8.1 ± 2.7 seconds following arterial detection, compared to 32.1 ± 5.4 seconds from contrast injection, representing a 62.1% reduction in the time-variability among subjects (N = 18). The real-time bolus-triggered technique more consistently captured the targeted arterial phase (94%), compared to the fixed timing technique (73%), representing an expected improvement of timing accuracy in 28% of patients (P = 0.0001389). CONCLUSION: Our results show detailed timing window analysis required for optimized arterial real-time bolus-triggering acquisition of transient arterial phase features of liver lesions, with optimized arterial triggering expected to improve reproducibility in a significant number of patients.

Nonlinear power loss during exercise in single-ventricle patients after the Fontan: insights from computational fluid dynamics.

BACKGROUND: We previously demonstrated that power loss (PL) through the total cavopulmonary connection (TCPC) in single-ventricle patients undergoing Fontan can be calculated by computational fluid dynamic analysis using 3-dimensional MRI anatomic reconstructions. PL through the TCPC may play a role in single-ventricle physiology and is a function of cardiac output. We hypothesized that PL through the TCPC increases significantly under exercise flow conditions. METHODS AND RESULTS: MRI data of 10 patients with a TCPC were analyzed to obtain 3-dimensional geometry and flow rates through the superior vena cava, inferior vena cava, left pulmonary artery, and right pulmonary artery. Steady computational fluid dynamic simulations were performed at baseline conditions using MRI-derived flows. Simulated exercise conditions of twice (2x) and three times (3x) baseline flow were performed by increasing inferior vena cava flow. PL, head loss, and effective resistance through the TCPC were calculated for each condition. Each condition was repeated at left pulmonary artery/right pulmonary artery ratios of 30/70 and 70/30 to determine the effects of pulmonary flow splits on exercise PL. For each patient, PL increases dramatically in a nonlinear fashion with increasing cardiac output, even when normalized to calculate head loss or resistance. Flow splits had a significant effect on PL at exercise, with most geometries favoring right pulmonary artery flow. CONCLUSIONS: The relationship between cardiac output and PL is nonlinear and highly dependent on TCPC geometry and pulmonary flow splits. This study demonstrates the importance of studying the TCPC under exercise conditions, because baseline conditions may not adequately characterize TCPC efficiency.

A new method for registration-based medical image interpolation.

A new technique is presented for interpolating between grey-scale images in a medical data set. Registration between neighboring slices is achieved with a modified control grid interpolation algorithm that selectively accepts displacement field updates in a manner optimized for performance. A cubic interpolator is then applied to pixel intensities correlated by the displacement fields. Special considerations are made for efficiency, interpolation quality, and compression in the implementation of the algorithm. Experimental results show that the new method achieves good quality, while offering dramatic improvement in efficiency relative to the best competing method.

Total cavopulmonary connection flow with functional left pulmonary artery stenosis: angioplasty and fenestration in vitro.

BACKGROUND: In our multicenter study of the total cavopulmonary connection (TCPC), a cohort of patients with long-segment left pulmonary artery (LPA) stenosis was observed (35%). The clinically recognized detrimental effects of LPA stenosis motivated a computational fluid dynamic simulation study within 3-dimensional patient-specific and idealized TCPC pathways. The goal of this study was to quantify and evaluate the hemodynamic impact of LPA stenosis and to judge interventional strategies aimed at treating it. METHODS AND RESULTS: Simulations were conducted at equal vascular lung resistance, modeling both discrete stenosis (DS) and diffuse long-segment hypoplasia with varying degrees of obstruction (0% to 80%). Models having fenestrations of 2 to 6 mm and atrium pressures of 4 to 14 mm Hg were explored. A patient-specific, extracardiac TCPC with 85% DS was studied in its original configuration and after virtual surgery that dilated the LPA to 0% stenosis in the computer medium. Performance indices improved exponentially (R2>0.99) with decreasing obstruction. Diffuse long-segment hypoplasia was approximately 50% more severe with regard to lung perfusion and cardiac energy loss than DS. Virtual angioplasty performed on the 3-dimensional Fontan anatomy exhibiting an 85% DS stenosis produced a 61% increase in left lung perfusion and a 50% decrease in cardiac energy dissipation. After 4-mm fenestration, TCPC baffle pressure dropped by approximately 10% and left lung perfusion decreased by approximately 8% compared with the 80% DS case. CONCLUSIONS: DS <60% and diffuse long-segment hypoplasia <40% could be considered tolerable because both resulted in only a 12% decrease in left lung perfusion. In contrast to angioplasty, a fenestration (right-to-left shunt) reduced TCPC pressure at the cost of decreased left and right lung perfusion. These results suggest that pre-Fontan computational fluid dynamic simulation may be valuable for determining both the hemodynamic significance of LPA stenosis and the potential benefits of intervention.

Colorectal Cancer Initial Diagnosis: Screening Colonoscopy, Diagnostic Colonoscopy, or Emergent Surgery, and Tumor Stage and Size at Initial Presentation.

INTRODUCTION/BACKGROUND: Rates of colorectal cancer screening are improving but remain suboptimal. Limited information is available regarding how patients are diagnosed with colorectal cancer (for example, asymptomatic screened patients or diagnostic workup because of the presence of symptoms). The purpose of this investigation was to determine how patients were diagnosed with colorectal cancer (screening colonoscopy, diagnostic colonoscopy, or emergent surgery) and tumor stage and size at diagnosis. PATIENTS AND METHODS: Adults evaluated between 2011 and 2014 with a diagnosis of colorectal cancer were identified. Clinical notes, endoscopy reports, surgical reports, radiology reports, and pathology reports were reviewed. Sex, race, ethnicity, age at the time of initial diagnosis, method of diagnosis, presenting symptom(s), and primary tumor size and stage at diagnosis were recorded. Colorectal cancer screening history was also recorded. RESULTS: The study population was 54% male (265 of 492) with a mean age of 58.9 years (range, 25-93 years). Initial tissue diagnosis was established at the time of screening colonoscopy in 10.7%, diagnostic colonoscopy in 79.2%, and during emergent surgery in 7.1%. Cancers diagnosed at the time of screening colonoscopy were more likely to be stage 1 than cancers diagnosed at the time of diagnostic colonoscopy or emergent surgery (38.5%, 7.2%, and 0%, respectively). Median tumor size was 3.0 cm for the screening colonoscopy group, 4.6 cm for the diagnostic colonoscopy group, and 5.0 cm for the emergent surgery group. At least 31% of patients diagnosed at the time of screening colonoscopy, 19% of patients diagnosed at the time of diagnostic colonoscopy, and 26% of patients diagnosed at the time of emergent surgery had never undergone a screening colonoscopy. CONCLUSION: Nearly 90% of colorectal cancer patients were diagnosed after development of symptoms and had more advanced disease than asymptomatic screening patients. Colorectal cancer outcomes will be improved by improving rates of colorectal cancer screening.

A Comprehensive CT Dose Reduction Program Using the ACR Dose Index Registry.

PURPOSE: The purpose of this article is to demonstrate the role of the ACR Dose Index Registry(®) (DIR) in a dose reduction program at a large academic health care system. METHODS: Using the ACR DIR, radiation doses were collected for four common CT examination types (head without contrast, chest with contrast, chest without contrast, and abdomen and pelvis with contrast). Baseline analysis of 7,255 CT examinations from seven scanners across the institution was performed for the period from December 1, 2011, to March 15, 2012. A comprehensive dose reduction initiative was guided by the identification of targets for dose improvement from the baseline analysis. Data for 14,938 examinations from the same seven scanners were analyzed for the postimplementation period of January 1, 2013, to July 1, 2013. RESULTS: The program included protocol changes, iterative reconstruction, optimization of scan acquisition, technologist education, and continuous monitoring with feedback tools. Average decrease in median dose-length product (DLP) across scanners was 30% for chest CT without contrast, 29% for noncontrast head CT, 26% for abdominal and pelvic CT with contrast, and 10% for chest CT with contrast. Compared with average median DLP in the ACR DIR, the median institution-wide CT DLPs after implementation were lower by 33% for chest CT without contrast, 32% for chest CT with contrast, 26% for abdominal and pelvic CT with contrast, and 6% for head CT without contrast. CONCLUSIONS: A comprehensive CT dose reduction program using the ACR DIR can lead to substantial dose reduction within a large health care system.

Gadolinium-enhanced imaging of liver tumors and manifestations of hepatitis: pharmacodynamic and technical considerations.

The ability for contrast-enhanced magnetic resonance imaging to provide significant diagnostic impact to focal and diffuse liver diseases requires knowledge, analysis, and technical optimization of the imaging techniques. Our review outlines the technical requirements needed to perform reproducible contrast-enhanced liver imaging and describes the important imaging features for assessing liver disease with conventional and alternate gadolinium-based contrast media. We present an experimental review of timing and quantification methods in dynamic contrast-enhanced liver imaging, with results of analysis showing perfusion and uptake curves in a series of patients and healthy subjects. An evidence-based methodology for reproducible arterial-phase imaging is detailed for performing a real-time bolus-tracking method. Additional diagnostic imaging features manifest at later imaging phases, in which the kinetic behavior of the contrast media serves to further specify focal lesions, while revealing detailed information of diffuse liver disease, particularly hepatic fibrosis. We review the utility of alternate gadolinium-based contrast media that undergo hepatocyte uptake, for applications related to liver tumor imaging. We also introduce results showing the potential for using alternate hepatocyte uptake agents to detect and quantify liver changes related to acute and chronic hepatitides.

Fontan hemodynamics: importance of pulmonary artery diameter.

OBJECTIVE: We quantify the geometric and hemodynamic characteristics of extracardiac and lateral tunnel Fontan surgical options and correlate certain anatomic characteristics with their hemodynamic efficiency and patient cardiac index. METHODS AND RESULTS: The study was conducted retrospectively on 22 patients undergoing Fontan operations (11 extracardiac and 11 lateral tunnel operations). Total cavopulmonary connection geometric parameters such as vessel areas, curvature, and offsets were quantified using a skeletonization method. Energy loss at the total cavopulmonary connection junction was available from previous in vitro experiments and computational fluid dynamic simulations for 5 and 9 patients, respectively. Cardiac index data were available for all patients. There was no significant difference in the mean and minimum cross-sectional vessel areas of the pulmonary artery between the extracardiac and lateral tunnel groups. The indexed energy dissipation within the total cavopulmonary connection was strongly correlated to minimum cross-sectional area of the pulmonary arteries (R(2) value of 0.90 and P < .0002), whereas all other geometric features, including shape characteristics, had no significant correlation. Finally, cardiac index significantly correlated with the minimum pulmonary artery area (P = .006), suggesting that total cavopulmonary connection energy losses significantly affect resting cardiac output. CONCLUSIONS: The minimum outlet size of the total cavopulmonary connection (ie, minimum cross section of pulmonary artery) governs the energy loss characteristics of the total cavopulmonary connection more strongly than variations in the shapes corresponding to extracardiac and lateral tunnel configurations. Differences in pulmonary artery sizes must be accounted for when comparing energy losses between extracardiac and lateral tunnel geometries.

Comparison of particle image velocimetry and phase contrast MRI in a patient-specific extracardiac total cavopulmonary connection.

Particle image velocimetry (PIV) and phase contrast magnetic resonance imaging (PC-MRI) have not been compared in complex biofluid environments. Such analysis is particularly useful to investigate flow structures in the correction of single ventricle congenital heart defects, where fluid dynamic efficiency is essential. A stereolithographic replica of an extracardiac total cavopulmonary connection (TCPC) is studied using PIV and PC-MRI in a steady flow loop. Volumetric two-component PIV is compared to volumetric three-component PC-MRI at various flow conditions. Similar flow structures are observed in both PIV and PC-MRI, where smooth flow dominates the extracardiac TCPC, and superior vena cava flow is preferential to the right pulmonary artery, while inferior vena cava flow is preferential to the left pulmonary artery. Where three-component velocity is available in PC-MRI studies, some helical flow in the extracardiac TCPC is observed. Vessel cross sections provide an effective means of validation for both experiments, and velocity magnitudes are of the same order. The results highlight similarities to validate flow in a complex patient-specific extracardiac TCPC. Additional information obtained by velocity in three components further describes the complexity of the flow in anatomic structures.

Modified control grid interpolation for the volumetric reconstruction of fluid flows.

Complex applications in fluid dynamics research often require more highly resolved velocity data than direct measurements or simulations provide. The advent of stereo PIV and PCMR techniques has advanced the state-of-the-art in flow velocity measurement, but 3D spatial resolution remains limited. Here a new technique is proposed for velocity data interpolation to address this problem. The new method performs with higher quality than competing solutions from the literature in terms of accurately interpolating velocities, maintaining fluid structure and domain boundaries, and preserving coherent structures.

Impaired power output and cardiac index with hypoplastic left heart syndrome: a magnetic resonance imaging study.

BACKGROUND: Unfavorable cardiac mechanics in children with hypoplastic left heart syndrome (HLHS) when compared with other single-ventricle defects may affect long-term morbidity and outcome. Using noninvasive phase contrast magnetic resonance imaging (PC MRI), we examined cardiac mechanics in children with HLHS and compared the results to other single-ventricle defects. METHODS: Eighteen children with HLHS and 18 children with other single-ventricle defects were studied after the Fontan operation. Phase contrast MRI scans were obtained perpendicular to the ascending aorta, and flow was quantified using an in-house segmentation and reconstruction scheme. The total power output was determined using the modified Bernoulli equation along with cardiac output and systemic vascular resistance index. RESULTS: Compared with non-HLHS congenital heart defects, children with HLHS had significantly lower power output (1.40 +/- 0.39 versus 1.78 +/- 0.38 W/m2, p < 0.004) and cardiac index (3.15 +/- 0.97 versus 4.09 +/- 1.23 L x Min(-1) x m(-2), p < 0.009) with a concomitant higher systemic vascular resistance index (28.94 +/- 11.5 versus 22.7 +/- 8.53 WU, p < 0.03) despite generating similar systolic blood pressures (112.9 +/- 22.4 versus 115.2 +/- 23 mm Hg, p > 0.05). CONCLUSIONS: Minimally invasive measurements with PC MRI in children with HLHS showed significantly lower power output and cardiac index when compared with other single-ventricle physiologies. Abnormal aortic flow patterns may contribute to power loss and may have long-term survival and morbidity implications associated with the Fontan procedure. Elevated systemic vascular resistance index despite similar blood pressure opens avenues for therapeutic intervention for afterload reduction.