Percutaneous endovascular tissue sampling of endoluminal tumors using directional atherectomy.

OBJECTIVES: To evaluate technical feasibility and safety of endovascular tumor specimen sampling using an escalating endovascular biopsy strategy using a directional atherectomy device compared with forceps biopsy and catheter aspiration. MATERIALS AND METHODS: Between 2013 and 2017, a cohort of ten consecutive patients (6 male; median age 56, range 39-73 years) was referred for sampling of endovascular masses. Localizations included the abdominal aorta (n = 4), left brachiocephalic vein (n = 2), inferior vena cava (n = 1), and left pulmonary artery (n = 3). For each individual mass, all three endovascular tissue sampling approaches were applied including catheter-based aspiration, straight two-jaw biopsy forceps, and directional atherectomy during a single session. RESULTS: Aspiration and forceps biopsy did not provide sufficient material for histological analyses. In contrast, technical success for endovascular tumor sampling using directional atherectomy was 100%. After two atherectomy passages, sufficient material was available for each vessel region allowing histologic diagnosis, which revealed sarcoma and chronic inflammation for masses in the aorta, angiosarcoma for brachiocephalic vein, hepatocellular carcinoma for inferior vena cava, and angiosarcoma for pulmonary artery. In case of a histologically benign diagnosis, no malignant tumor proliferation was obvious on follow-up imaging studies after 3 months and 1 year. Thus, the rate of false-negative results was considered 0%. No procedure-associated complications, e.g., vessel perforation, were recorded. CONCLUSION: Preliminary results in a limited number of patients proved directional atherectomy beneficial as a safe and feasible technique for endoluminal tissue sampling of vascular masses. Additional large-scale studies are necessary and worthy for further evaluation in clinical practice. KEY POINTS: • Endovascular masses pose a challenge to appropriate clinical management. • Off-label directional atherectomy proved to be a safe and feasible technique for endoluminal tissue sampling of vascular masses. Furthermore, directional atherectomy was superior to aspiration or forceps biopsy in our small study cohort. • Directional atherectomy may represent the last or only option for tissue probing as a prerequisite for further treatment decisions.

Organ-Preserving Surgical Treatment of a Horseshoe Kidney Occupied by a Large Renal Cell Carcinoma with Extensive Venous Invasion: A Case Report.

The horseshoe kidney is one of the most common congenital disorders affecting the urogenital system. Following a fusion of the lower kidney poles, which in turn lead to the formation of an isthmus, this anatomical variation is accompanied by other characteristic properties like an incomplete ascension, ventral rotation of the pelvices as well as atypical vascular supply. Even though renal carcinoids and Wilms tumors are more common in horseshoe kidneys, the incidence of renal cell carcinomas seems to be unaffected. Here we report the case of a locally advanced renal cell carcinoma with extensive venous invasion occurring in a horseshoe kidney and its complex surgical management. The whole primary tumor as well as a majority of venous tumor thrombi could be removed by a combination of 2/3 nephrectomy and cavotomy with thrombectomy. During 1 year of follow-up, the patient neither suffered from a tumor relapse, nor did he require renal replacement therapy. Thus, we conclude that even in cases of RCC where advanced disease is associated with complex anatomical situations, organ-preserving surgical treatment should be pursued to achieve excellent functional and oncological results.

Right and Left Ventricular Function and Mass in Male Elite Master Athletes: A Controlled Contrast-Enhanced Cardiovascular Magnetic Resonance Study.

BACKGROUND: It is under debate whether the cumulative effects of intensive endurance exercise induce chronic cardiac damage, mainly involving the right heart. The aim of this study was to examine the cardiac structure and function in long-term elite master endurance athletes with special focus on the right ventricle by contrast-enhanced cardiovascular magnetic resonance. METHODS AND RESULTS: Thirty-three healthy white competitive elite male master endurance athletes (age range, 30-60 years) with a training history of 29±8 years, and 33 white control subjects pair-matched for age, height, and weight underwent cardiopulmonary exercise testing, echocardiography including tissue-Doppler imaging and speckle tracking, and cardiovascular magnetic resonance. Indexed left ventricular mass and right ventricular mass (left ventricular mass/body surface area, 96±13 and 62±10 g/m(2); P<0.001; right ventricular mass/body surface area, 36±7 and 24±5 g/m(2); P<0.001) and indexed left ventricular end-diastolic volume and right ventricular end-diastolic volume (left ventricular end-diastolic volume/body surface area, 104±13 and 69±18 mL/m(2); P<0.001; right ventricular end-diastolic volume/body surface area, 110±22 and 66±16 mL/m(2); P<0.001) were significantly increased in athletes in comparison with control subjects. Right ventricular ejection fraction did not differ between athletes and control subjects (52±8 and 54±6%; P=0.26). Pathological late enhancement was detected in 1 athlete. No correlations were found for left ventricular and right ventricular volumes and ejection fraction with N-terminal pro-brain natriuretic peptide, and high-sensitive troponin was negative in all subjects. CONCLUSIONS: Based on our results, chronic right ventricular damage in elite endurance master athletes with lifelong high training volumes seems to be unlikely. Thus, the hypothesis of an exercise-induced arrhythmogenic right ventricular cardiomyopathy has to be questioned.

First report of an aneurysmal bone cyst presenting as subungual mass.

Painful subungual tumor masses in the toes usually emerge as glomus tumors or subungual exostoses. We present a patient with an aneurysmal bone cyst located subungually in whom the diagnosis was delayed due to inadequate diagnostic procedures, which led to marked destruction of the distal phalanx of the great toe of the right foot. After biopsy, the distal phalanx could not be preserved due to critical soft tissue involvement and the size of the process. Thus, we describe this rare entity to encourage clinicians to establish the diagnosis by biopsy of a tissue swelling of unclear origin and duration that does not resolve after a short time. Imaging examinations are useful in demonstrating periosteal involvement and extension of the lesion and can be helpful in the diagnostic algorithm. An interdisciplinary approach is a top priority to ensure optimal treatment.

Effect of renal denervation on left ventricular mass and function in patients with resistant hypertension: data from a multi-centre cardiovascular magnetic resonance imaging trial.

AIMS: Sympathetic stimulation induces left ventricular hypertrophy and is associated with increased cardiovascular risk. Catheter-based renal denervation (RDN) has been shown to reduce sympathetic outflow and blood pressure (BP). The present multi-centre study aimed to investigate the effect of RDN on anatomic and functional myocardial parameters, assessed by cardiac magnetic resonance (CMR), in patients with resistant hypertension. METHODS AND RESULTS: Cardiac magnetic resonance was performed in 72 patients (mean age 66 ± 10 years) with resistant hypertension (55 patients underwent RDN, 17 served as controls) at baseline and after 6 months. Clinical data and CMR results were analysed blindly. Renal denervation significantly reduced systolic and diastolic BP by 22/8 mm Hg and left ventricular mass index (LVMI) by 7.1% (46.3 ± 13.6 g/m(1.7) vs. 43.0 ± 12.6 g/m(1.7), P < 0.001) without changes in the control group (41.9 ± 10.8 g/m(1.7) vs. 42.0 ± 9.7 g/m(1.7), P = 0.653). Ejection fraction (LVEF) in patients with impaired LVEF at baseline (<50%) significantly increased after RDN (43% vs. 50%, P < 0.001). Left ventricular circumferential strain as a surrogate of diastolic function in the subgroup of patients with reduced strain at baseline increased by 21% only in the RDN group (-14.8 vs. -17.9; P = 0.001) and not in control patients (-15.5 vs. -16.4, P = 0.508). CONCLUSIONS: Catheter-based RDN significantly reduced BP and LVMI and improved EF and circumferential strain in patients with resistant hypertension, occurring partly BP independently.

[Innovations in the classification of soft tissue tumors]. / Neuerungen in der Klassifikation von Weichteiltumoren.

Soft tissue tumors are a very heterogeneous group of tumors. Their classification is regularly updated by the World Health Organization (WHO), most recently in 2020. The current classification of soft tissue tumors emphasizes molecular biological tumor characteristics, which enable tumor-specific treatment. In addition to Ewing's sarcoma, which occurs as bone as well as extra-skeletal soft tissue tumors as a small round cell sarcoma, three other subtypes of undifferentiated, small and round cell sarcomas have been introduced. Some names of the new sarcomas can be derived from the gene mutations. The groups of adipocytic and (myo)fibroblastic tumors have been extended by three further entities. There were further additions to vascular soft tissue tumors, smooth muscle cell tumors, peripheral nerve sheath tumors and tumors of uncertain differentiation. A distinction is made between benign, intermediate locally aggressive, intermediate rarely metastatic and malignant soft tissue tumors.

A novel entity of massive multifocal osteolyses in the elderly.

Osteolyses are common findings in elderly patients and most frequently represent malignant or locally aggressive bone tumors, infection, inflammatory and endocrine disorders, histiocytoses, and rare diseases such as Gorham-Stout syndrome. We here report on a novel entity of massive multifocal osteolyses in both shoulders, the right hip and left knee joint and the dens of an 83-year-old patient not relatable to any previously known etiopathology of bone disorders. The soft tissue mass is of myxoid stroma with an unspecific granulomatous inflammatory process, aggressively destroying extensive cortical and cancellous bone segments and encroaching on articulating bones in diarthrodial large joints. Radiological, nuclear medical, serological, histological, and immunohistochemical analyses were incapable of further classifying the disease pattern within the existing scheme of pathology. Quantitative polymerase chain reaction and next generation sequencing revealed that mutations are not suggestive of any known hereditary or acquired bone disease. Possible treatment options include radionuclide therapy for pain palliation and percutaneous radiation to arrest bone resorption while surgical treatment is inevitable for pathological fractures. This case study shall increase the awareness of the musculoskeletal community and motivate to collect further information on this rare but mutilating disorder.

Calf bioimpedance spectroscopy for determination of dry weight in hemodialysis patients: effects on hypertension and left ventricular hypertrophy.

BACKGROUND/AIMS: Dry weight estimation in hemodialysis patients is still a substantial problem. Despite meticulous clinical assessment, fluid overload is common, leading to hypertension and left ventricular hypertrophy (LVH). Segmental calf bioimpedance spectroscopy (cBIS) is a novel tool for dry weight assessment. Here we tested the hypothesis, that its clinical routine use reduces arterial hypertension and left ventricular mass. METHODS: Left ventricular mass (determined by magnetic resonance imaging), blood pressure and antihypertensive medication (defined daily doses, ddd) were assessed at baseline (BL). Thereafter post-dialytic target weight was reduced until cBIS-defined dry weight was reached (DW). During a 6-month follow up, DW was re-evaluated monthly by cBIS and end-dialytic weight was adjusted correspondingly. At the end, left ventricular mass, blood pressure and antihypertensive medication were determined a 3rd time (follow-up, FU). RESULTS: Eleven out of 15 patients were available for analysis after 6 months. Left ventricular mass showed a declining trend during the study period (Mean±SD; BL 145±54 g; DW 142±55 g; FU 137±52 g; p=0.61, linear mixed model). Comparable results were obtained for systolic blood pressure (BL 158±18 mmHg; DW 144±19 mmHg; FU 149±21 mmHg; p=0.07), and antihypertensive medication (BL 3.28±2.82ddd; DW 2.86±2.81ddd; FU 3.36±3.05ddd; p=0.37). CONCLUSIONS: We conclude that attainment of dry weight assessed by cBIS tends to reduce left ventricular mass and blood pressure while antihypertensive medication remains unchanged. While the study was underpowered, its results provide an important hypothesis generating data basis for the design of larger studies.

Subacute liver failure by pseudocirrhotic metastatic breast cancer infiltration.

Hepatic metastases are common in the clinical course of breast cancer and typically appear as mass lesions. This report describes the case of a 70-year-old woman with a history of breast cancer and no previously known liver disease presenting with the first episode of variceal bleeding and subacute hepatic failure. Imaging studies indicated liver cirrhosis without signs of malignant focal lesions. Comprehensive diagnostic work-up was negative for specific causes of liver disease and provided no evidence for tumor recurrence. Finally transjugular liver biopsy revealed a marked diffuse desmoplastic infiltration by breast cancer cells. Malignant pseudocirrhosis is an unusual pattern of metastatic, tumor spread representing a rare but important differential diagnosis of progressive liver failure. Liver biopsy is the key procedure to establish the diagnosis as imaging studies may mimic cirrhosis.

Improvement of Groin Pain in a Football Player with Femoroacetabular Impingement via a Correction of the Pelvic Position-A Case Report.

Background: Femoroacetabular impingement is one possible cause for groin pain and can lead to long periods of absence for football players. In cam impingement, the end-grade position of the leg at kicking makes the hip particularly prone to faulty contact between the acetabulum and the femoral head. Studies suggest that the resting position of the pelvis in the sagittal plane may have an important role in the biomechanics of movement in the presence of cam impingement. Methods: A 19-year-old male competitive footballer complained of sudden groin pain during a period of low athletic load. Biomechanical tests (3D posture and isometric strength analyses) showed that unbalanced individual strength training had resulted in an increased forward tilt of the pelvis. At the same time, cam impingement was confirmed radiologically, which obviously contributed to the sudden onset of the symptoms. The kicking technique of the athlete showed increased hip and trunk flexion, which also indicated a muscular imbalance. Targeted strength and stretching exercises three times a week improved the pelvic position in terms of reduced anteversion. At the same time, the patient performed strength exercises to improve his kicking technique. Results: After 8 weeks, improvements in his pelvic position and global posture and increased muscle strength could be verified. At the same time, the athlete was free of complaints again. Conclusions: When groin pain occurs in football players with cam impingement, special attention should be paid to the resting position of the pelvis in the sagittal plane. Correcting increased pelvic anteversion can prevent unfavourable end-grade collisions of the acetabulum and femoral head during kicking with strong hip flexion and adduction. Possible changes in the pelvic position due to adverse individual strength training performed by young athletes should always be kept in mind.

First live birth after uterine transposition.

OBJECTIVE: To our knowledge, to report the first case of live birth of a child after uterine transposition (UT), pelvic radiotherapy, and subsequent uterine repositioning. DESIGN: Case report. SETTING: Tertiary referral cancer hospital. PATIENT(S): A 28-year-old nulligravid woman with left iliac and thoracic synchronous myxoid low-grade liposarcoma, which was resected with close margins. INTERVENTION(S): The patient underwent UT before undergoing pelvic (60 Gy) and thoracic (60 Gy) radiation on October 25, 2018. After radiotherapy, her uterus was reimplanted in the pelvis on February 20, 2019. MAIN OUTCOME MEASURE(S): The patient became pregnant in June 2021 and experienced an uneventful pregnancy until 36 weeks, when the patient started preterm labor and had a cesarean section delivery on January 26, 2022. RESULT(S): A boy was delivered after a gestation period of 36 weeks and 2 days (2686 g and 46.5 cm), with Apgar scores of 5 and 9, respectively; both mother and child were discharged the following day. After 1 year of follow-ups, the infant maintained normal development and the patient showed no signs of recurrence. CONCLUSION(S): To our knowledge, this case of the first live birth after UT is a proof-of-concept for the viability of UT as a procedure to prevent infertility in patients requiring pelvic radiotherapy.

Diffusion-weighted MRI improves response assessment after definitive radiotherapy in patients with NSCLC.

BACKGROUND: Computed tomography (CT) is the standard procedure for follow-up of non-small-cell lung cancer (NSCLC) after radiochemotherapy. CT has difficulties differentiating between tumor, atelectasis and radiation induced lung toxicity (RILT). Diffusion-weighted imaging (DWI) may enable a more accurate detection of vital tumor tissue. The aim of this study was to determine the diagnostic value of MRI versus CT in the follow-up of NSCLC. METHODS: Twelve patients with NSCLC stages I-III scheduled for radiochemotherapy were enrolled in this prospective study. CT with i.v. contrast agent and non enhanced MRI were performed before and 3, 6 and 12 months after treatment. Standardized ROIs were used to determine the apparent diffusion weighted coefficient (ADC) within the tumor. Tumor size was assessed by the longest longitudinal diameter (LD) and tumor volume on DWI and CT. RILT was assessed on a 4-point-score in breath-triggered T2-TSE and CT. RESULTS: There was no significant difference regarding LD and tumor volume between MRI and CT (p ≥ 0.6221, respectively p ≥ 0.25). Evaluation of RILT showed a very high correlation between MRI and CT at 3 (r = 0.8750) and 12 months (r = 0.903). Assessment of the ADC values suggested that patients with a good tumor response have higher ADC values than non-responders. CONCLUSIONS: DWI is equivalent to CT for tumor volume determination in patients with NSCLC during follow up. The extent of RILT can be reliably determined by MRI. DWI could become a beneficial method to assess tumor response more accurately. ADC values may be useful as a prognostic marker.

Effects of selective heart rate reduction with ivabradine on LV function and central hemodynamics in patients with chronic coronary syndrome.

OBJECTIVES: We assessed left ventricular (LV) function and central hemodynamic effects in patients with a heart rate (HR) at rest of ≥70 beats per minute (bpm) and chronic coronary syndrome (CCS) after long-term treatment with ivabradine compared to placebo by cardiac magnetic resonance (CMR) imaging. METHODS AND RESULTS: In a randomized, double-blinded, prospective cross-over design, 23 patients (18 male, 5 female) were treated with ivabradine (7.5 mg bid) or placebo for 6 months. CMR imaging was performed at baseline and after 6 and 12 months to determine LV functional parameters.Mean resting HR on treatment with ivabradine was 58 ± 8.2 bpm and 70.2 ± 8.3 bpm during placebo (p < 0.0001).There was no difference in systolic LV ejection fraction (ivabradine 57.4 ± 11.2% vs placebo 53.0 ± 10.9%, p = 0.18), indexed end-diastolic (EDVi) or end-systolic volumes (ESVi). Indexed stroke volume (SVi) (ml/m2) remained unchanged after treatment with ivabradine. Volume time curve parameters reflecting systolic LV function (peak ejection rate and time) were unaffected by ivabradine, while both peak filling rate (PFR) and PFR/EDV were significantly increased. Mean aortic velocity (cm/s) was significantly reduced during treatment with ivabradine (ivabradine 6.7 ± 2.7 vs placebo 9.0 ± 3.4, p = 0.01). Aortic flow parameters were correlated to parameters of vascular stiffness. The strongest correlation was revealed for mean aortic velocity with aortic distensibility (AD) (r = -0.86 [-0.90 to -0.85], p < 0.0001). CONCLUSION: Long-term reduction of HR with ivabradine in patients with CCS improved diastolic function and reduced mean aortic flow velocity.

Effects of heart rate reduction with ivabradine on vascular stiffness and endothelial function in chronic stable coronary artery disease.

INTRODUCTION: Epidemiological and clinical studies have shown a relevant association between heart rate and cardiovascular mortality. Experimental studies identified vascular effects of heart rate reduction with the If channel inhibitor ivabradine. Therefore, the effects of heart rate reduction on endothelial function and indices of arterial stiffness were examined in patients with stable coronary artery disease in a prospective, placebo-controlled clinical crossover study. METHODS AND RESULTS: Twenty-three patients (18 men and 5 women) with a resting heart rate (HR) of at least 70 beats per minute (bpm) and stable coronary artery disease were enrolled in this study. In a cross-over design, all patients were treated with ivabradine (Iva, 7.5 mg b.i.d.) and placebo for 6 months each. Iva reduced heart rate by 11.4 bpm (Iva 58.8 ±â€Š8.2 bpm vs. placebo 70.2 ±â€Š8.3 bpm, P < 0.0001). Augmentation index (AIx75), carotid-femoral pulse wave velocity (cfPWV) and central aortic blood pressure were measured using applanation tonometry (SphygmoCor). HRR by Iva increased AIx75 by 12.4% (Iva 24.3 ±â€Š10.5% vs. placebo 21.3 ±â€Š10.1%, P < 0.05) and reduced cfPWV by 14.1% (Iva 6.3 ±â€Š1.7 m/s vs. placebo 7.3 ±â€Š1.4 m/s, P < 0.01). Iva increased mean central blood pressure by 7.8% (Iva 107.5 ±â€Š15.4 mmHg vs. placebo 99.1 ±â€Š12.2 mmHg, P < 0.001). Endothelial function was determined measuring the flow-mediated vasodilation (FMD) of the brachial artery. HRR by Iva increased FMD by 18.5% (Iva 7.3 ±â€Š2.2% vs. placebo 6.0 ±â€Š2.0%, P < 0.001). Aortic distensibility was characterized by MRI. HRR by Iva increased aortic distensibility by 33.3% (Iva 0.003 ±â€Š0.001/mmHg vs. placebo 0.002 ±â€Š0.010/mmHg, P < 0.01) and circumferential cyclic strain by 37.1% (Iva 0.062 ±â€Š0.027 vs. placebo 0.039 ±â€Š0.018, P < 0.0001). CONCLUSION: Heart rate reduction with Iva increased endothelium-dependent vasodilation and reduced arterial stiffness in patients with stable CAD. These findings corroborate and expand the results collected in experimental studies and indicate the importance of heart rate as a determinant of vascular function.

Evaluation of Gadopiclenol and P846, 2 High-Relaxivity Macrocyclic Magnetic Resonance Contrast Agents Without Protein Binding, in a Rodent Model of Hepatic Metastases: Potential Solutions for Improved Enhancement at Ultrahigh Field Strength.

PURPOSE: The aim of this study was to evaluate in vitro and in vivo the enhancement properties of experimental gadolinium (Gd)-based contrast agents (GBCAs) with different molecular weights and hydration numbers (P846 and gadopiclenol) compared with clinically approved low-molecular, extracellular agents (gadopentetate and gadoterate) at 9.4 T and to discuss influencing factors on r1 relaxivities. METHODS AND MATERIALS: All experiments were performed with a 9.4 T animal scanner (Bruker, Germany). We performed relaxometry measurements for all contrast agents in human plasma at 37°C using an IR-RARE sequence. In addition, we compared P846 with gadopentetate and gadopiclenol with gadoterate intraindividually in rats with hepatic colorectal cancer metastases (n = 10 each) acquiring T1-weighted FLASH sequences before and at 10 consecutive time points during 20 minutes. After intravenous contrast agent application, signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and lesion enhancement (LE) for liver parenchyma and tumors were calculated based on region of interest measurements. RESULTS: Longitudinal relaxivities (r1) of the low-molecular agents were lower as compared with the experimental compounds. However, r1 of gadopentetate and gadoterate demonstrated only a moderate decrease of r1 at 9.4 T as compared with known data at lower field strengths (gadopentetate: r1 [at 9.4 T], 3.4 mM s/r1 [at 1.5 T], 4.1 mM s/gadoterate: r1 [at 9.4 T], 3.1 mM s/r1 [at 1.5 T], 3.6 mM s). In contrast, r1 of P846 showed a marked reduction at 9.4 T compared with 1.5 T (P846: r1 [at 9.4 T], 6.4 mM s/r1 [at 1.5 T], 32 mM s). Gadopiclenol provided the highest r1 in this study at 9.4 T and the drop of r1 as compared with lower field strength is less apparent (gadopiclenol: r1 [at 9.4 T], 8.7 mM s/r1 [at 1.5 T], 12.7 mM s).In vivo, P846 and gadopiclenol showed significantly higher SNR, CNR, and LE as compared with the low-molecular control agents (mean ± SD; SNRliver [gadopentetate, 18.1 ± 1.2; P846, 27.2 ± 1.5; P < 0.001]; SNRtumor [gadopentetate, 22.6 ± 1.9; P846, 40.1 ± 1.9; P < 0.001]; CNR [gadopentetate, 4.6 ± 1.0; P846, 12.9 ± 0.9; P < 0.001]; LE [gadopentetate, 7.2 ± 1.9; P846, 14.9 ± 1.9; P < 0.001]/SNRliver [gadoterate, 8.8 ± 0.5; gadopiclenol, 12.6 ± 1.3; P < 0.001]; SNRtumor [gadoterate, 11.3 ± 1.2; gadopiclenol, 20.9 ± 2.9; P < 0.001]; CNR [gadoterate, 2.5 ± 0.7; gadopiclenol, 8.3 ± 1.7; P < 0.001]; LE [gadoterate, 4.4 ± 1.2; gadopiclenol, 13.0 ± 2.9; P < 0.001]). Thus, for equal Gd doses, gadopiclenol and P846 increase the CNR of liver metastases by a factor of 2.5 to 3 at 9.4 T compared with gadoterate and gadopentetate. CONCLUSIONS: P846 and gadopiclenol provide superior enhancement at 9.4 T as compared with gadopentetate and gadoterate. However, the macromolecular agent P846 shows a marked decrease of r1 from 1.5 T to 9.4 T. This effect is less apparent for the low-molecular agents gadopiclenol, gadopentetate, and gadoterate. Yet, based on the higher hydration number, r1 of P846 and gadopiclenol are markedly higher as compared with the reference contrast agents. Thus, building compounds with moderately increased molecular size and hydration number, as implemented in gadopiclenol, seems to be a promising way to develop highly effective GBCAs.Advantages for gadopiclenol include a strong enhancement regardless of the external magnetic field strength, pharmacokinetics comparable to those of clinically approved extracellular GBCAs, and the potential to either improve sensitivity in diagnostic magnetic resonance imaging by improving lesion conspicuity or to perform studies with significantly reduced Gd-dose while at the same time providing comparable diagnostic accuracy. However, all this needs to be proven in clinical studies.

Renal artery stenosis evaluation: diagnostic performance of gadobenate dimeglumine-enhanced MR angiography--comparison with DSA.

PURPOSE: To prospectively determine diagnostic performance and safety of contrast material-enhanced (CE) magnetic resonance (MR) angiography with 0.1 mmol per kilogram of body weight gadobenate dimeglumine for depiction of significant steno-occlusive disease (> or =51% stenosis) of renal arteries, with digital subtraction angiography (DSA) as reference standard. MATERIALS AND METHODS: This multicenter study was approved by local institutional review boards; all patients provided written informed consent. Patient enrollment and examination at centers in the United States complied with HIPAA. Two hundred ninety-three patients (154 men, 139 women; mean age, 61.0 years) with severe hypertension (82.2%), progressive renal failure (11.3%), and suspected renal artery stenosis (6.5%) underwent CE MR angiography with three-dimensional spoiled gradient-echo sequences after administration of 0.1 mmol/kg gadobenate dimeglumine at 2 mL/sec. Anteroposterior and oblique DSA was performed in 268 (91.5%) patients. Three independent blinded reviewers evaluated CE MR angiographic images. Sensitivity, specificity, and accuracy of CE MR angiography for detection of significant steno-occlusive disease (> or =51% vessel lumen narrowing) were determined at segment (main renal artery) and patient levels. Positive and negative predictive values and positive and negative likelihood ratios were determined. Interobserver agreement was analyzed with generalized kappa statistics. A safety evaluation (clinical examination, electrocardiogram, blood and urine analysis, monitoring for adverse events) was performed. RESULTS: Of 268 patients, 178 who were evaluated with MR angiography and DSA had significant steno-occlusive disease of renal arteries at DSA. Sensitivity, specificity, and accuracy of CE MR angiography for detection of 51% or greater stenosis or occlusion were 60.1%-84.1%, 89.4%-94.7%, and 80.4%-86.9%, respectively, at segment level. Similar values were obtained for predictive values and for patient-level analyses. Few CE MR angiographic examinations (1.9%-2.8%) were technically inadequate. Interobserver agreement for detection of significant steno-occlusive disease was good (79.9% agreement; kappa = 0.69). No safety concerns were noted. CONCLUSION: CE MR angiography performed with 0.1 mmol/kg gadobenate dimeglumine, compared with DSA, is safe and provides good sensitivity, specificity, and accuracy for detection of significant renal artery steno-occlusive disease.

Evaluation of a novel time-efficient protocol for gadobenate dimeglumine (Gd-BOPTA)-enhanced liver magnetic resonance imaging.

OBJECTIVE: We sought to evaluate gadobenate dimeglumine for the detection and characterization of focal liver lesions in the unenhanced and already pre-enhanced liver. MATERIALS AND METHODS: Sixty patients were evaluated prospectively. Unenhanced T1-weighted gradient echo (T1wGRE) and T2-weighted turbo spin echo (T2wTSE) images were acquired followed by contrast-enhanced T1wGRE images during the dynamic, equilibrium, and delayed phases after the bolus injection of 0.05 mmol/kg gadobenate dimeglumine. An identical series of dynamic images was then acquired after the delayed scan following a second 0.05 mmol/kg bolus of gadobenate dimeglumine. Images were evaluated randomly in 2 sessions by 3 independent blinded readers. Evaluated images in the first session comprised the unenhanced images, the first or second set of dynamic images, and the delayed images. The second session included the unenhanced images, the dynamic images not yet evaluated in the first session, and the delayed images. The 2 reading sessions were compared for lesion characterization and diagnosis, and kappa (kappa) values for interobserver agreement were determined. Quantitative evaluation of lesion contrast enhancement was also performed. RESULTS: The enhancement behavior in the second dynamic series was similar to that in the first series, although pre-enhancement of the normal liver resulted in reduced lesion-liver contrast-to-noise ratios and the visualization of some lesions only on arterial phase images. Typical imaging features for the lesions included in the study were visualized clearly in both series. Strong agreement (kappa=0.56-0.89; all evaluations) between the 2 images sets was noted by all readers for differentiation of benign from malignant lesions and for definition of specific diagnosis, and between readers for diagnoses established based on images acquired in the unenhanced and pre-enhanced liver. CONCLUSION: Dynamic imaging in the hepatobiliary phase gives similar information as dynamic imaging of the unenhanced liver. This might prove advantageous for screening protocols involving same session imaging of primary extrahepatic tumors and liver.

Diagnostic performance of gadobenate dimeglumine enhanced MR angiography of the iliofemoral and calf arteries: a large-scale multicenter trial.

OBJECTIVE: The purpose of this study was to compare gadobenate dimeglumine-enhanced MR angiography and unenhanced time-of-flight MR angiography for the detection of significant peripheral arterial occlusive disease using digital subtraction angiography as our reference standard. SUBJECTS AND METHODS: Two hundred seventy-two patients underwent MR angiography and digital subtraction angiography of the iliofemoral arteries. MR angiography was performed before (2D time-of-flight acquisitions) and after (spoiled gradient-echo acquisitions) the administration of 0.1 mmol/kg of gadobenate dimeglumine at 1-2 mL/s. Contrast-enhanced MR angiography and digital subtraction angiography of the calf arteries were performed in 241 of 272 participants. Images were evaluated on-site and by four blinded reviewers (three for MR angiography, one for digital subtraction angiography). Comparative diagnostic performance for the detection of significant (> or = 51% vessel lumen narrowing) disease was evaluated using the McNemar test and generalized estimating equations. Interobserver agreement was assessed with generalized kappa statistics. The chi-square test was used to compare technical failure rates. RESULTS: Digital subtraction angiography confirmed significant disease (597 stenoses, 386 occlusions) in 983 iliofemoral segments. The sensitivity (54-80.9%), specificity (89.7-95.3%), and accuracy (85-87.5%) of contrast-enhanced MR angiography for the detection of significant iliofemoral disease were significantly (p < 0.001, all reviewers) better than those of time-of-flight MR angiography (33.2-62.8%, 74.3-88.9%, and 68-77.3%, respectively). Similar diagnostic performance was obtained for the calf arteries. The technical failure rate with contrast-enhanced MR angiography (2.5-3.4%) was similar to that of digital subtraction angiography (1.4%) and significantly (p < 0.001) lower than that of time-of-flight MR angiography (6.2-18.0%). Significantly better reproducibility (p < 0.001) was obtained with contrast-enhanced MR angiography (82% vs 65.2% agreement; kappa = 0.66 vs 0.45). CONCLUSION: Improved diagnostic performance and reproducibility are achievable with gadobenate dimeglumine-enhanced MR angiography in patients with peripheral arterial occlusive disease.

Effects of Liver Fibrosis Progression on Tissue Relaxation Times in Different Mouse Models Assessed by Ultrahigh Field Magnetic Resonance Imaging.

Recently, clinical studies demonstrated that magnetic resonance relaxometry with determination of relaxation times T1 and T2⁎ may aid in staging and management of liver fibrosis in patients suffering from viral hepatitis and steatohepatitis. In the present study we investigated T1 and T2⁎ in different models of liver fibrosis to compare alternate pathophysiologies in their effects on relaxation times and to further develop noninvasive quantification methods of liver fibrosis. MRI was performed with a fast spin echo sequence for measurement of T1 and a multigradient echo sequence for determination of T2⁎. Toxic liver fibrosis was induced by injections of carbon tetrachloride (1.4 mL CCl4 per kg bodyweight and week, for 3 or 6 weeks) in BALB/cJ mice. Chronic sclerosing cholangitis was mimicked using the ATP-binding cassette transporter B4 knockout (Abcb4 -/-) mouse model. Untreated BALB/cJ mice served as controls. To assess hepatic fibrosis, we ascertained collagen contents and fibrosis scores after Sirius red staining. T1 and T2⁎ correlate differently to disease severity and etiology of liver fibrosis. T2⁎ shows significant decrease correlating with fibrosis in CCl4 treated animals, while demonstrating significant increase with disease severity in Abcb4 -/- mice. Measurements of T1 and T2⁎ may therefore facilitate discrimination between different stages and causes of liver fibrosis.