Dynamic changes in tumor profiling reveal intra- and inter-tumoral heterogeneity focused on an uncharacterized HER2 mutation: a case report of a young breast cancer patient.

Despite multiple recent advances in systemic therapy for metastatic breast cancer, cases which display suboptimal response to guideline-driven treatment are frequently seen in the clinic. Effective options for such patients are limited, particularly in later line of therapy, and selection of optimal treatment options is essentially empirical and based largely on considerations of previous regimens received. Comprehensive cancer profiling includes detection of genetic alterations in tissue and circulating tumor DNA (ctDNA), immunohistochemistry (IHC) from re-biopsied metastatic disease, circulating tumor cells (CTCs), gene expression analysis and pharmacogenomics. The advent of this methodology and application to metastatic breast cancer, facilitates a more scientifically informed approach to identification of optimal systemic therapy approaches independent of the restrictions implied by clinical guidelines. Here we describe a case of metastatic breast cancer where consecutive comprehensive tumor profiling reveals ongoing tumor evolution, guiding the identification of novel effective therapeutic strategies.

Imaging of clinically silent rectoprostatic hematoma in MRI guided in-bore prostate biopsy.

MR imaging provides awareness for rectoprostatic hematomas as a complication in prostate biopsy. We evaluated the frequency and size of clinically silent bleeding after in-bore MRI-guided prostate biopsy according to documentation in MRI. From 2007 until 2020 in-bore MRI-guided prostate biopsy was performed in 283 consecutive patients with suspected prostate cancer. Interventional image documentation was reviewed for rectoprostatic hematomas and rectal blood collections in this retrospective observational single-center study. Correlation to patient characteristics was analyzed using a multivariable logistic regression model. 283 consecutive patients with a mean age of 66 ± 8 years were included. We diagnosed bleeding complications in 41 (14.5%) of the patients. Significant rectoprostatic hematomas were found in 24 patients. Intra-rectal blood collections were observed in 16 patients and one patient showed bleeding in the urinary bladder. The volume of rectoprostatic hematomas was determined with a median of 7.5 ml (range 2-40 ml, IQR 11.25). We found no correlation between the presence of a rectoprostatic hematoma and malignant findings, patient position in biopsy, number of cores, age, prostate volume nor PSA density (p > 0.05). Rectoprostatic hematomas and rectal blood collections are rare complications after in-bore MR-guided prostate biopsy. MR imaging provides benefits not only for lesion detection in prostate biopsy but also for the control of bleeding complications, which can be overlooked in standard TRUS biopsy. Their significance in pain, erectile dysfunction, and urinary retention remains to be investigated.

Structured reporting in radiologic education - Potential of different PI-RADS versions in prostate MRI controlled by in-bore MR-guided biopsies.

OBJECTIVES: To evaluate the efficiency of structured reporting in radiologic education - based on the example of different PI-RADS score versions for multiparametric MRI (mpMRI) of the prostate. METHODS: MpMRI of 688 prostate lesions in 180 patients were retrospectively reviewed by an experienced radiologist and by a student using PI-RADS V1 and V2. Data sets were reviewed for changes according to PI-RADS V2.1. The results were correlated with results obtained by MR-guided biopsy. Diagnostic potency was evaluated by ROC analysis. Sensitivity, specificity and correct-graded samples were evaluated for different cutpoints. The agreement between radiologist and student was determined for the aggregation of the PI-RADS score in three categories. The student's time needed for evaluation was measured. RESULTS: The area under curve of the ROC analysis was 0.782/0.788 (V1/V2) for the student and 0.841/0.833 (V1/V2) for the radiologist. The agreement between student and radiologist showed a Cohen's weighted κ coefficient of 0.495 for V1 and 0.518 for V2. Median student's time needed for score assessment was 4:34 min for PI-RADSv1 and 2:00 min for PI-RADSv2 (p < 0.001). Re-evaluation for V2.1 changed the category in 1.4% of all ratings. CONCLUSION: The capacity of prostate cancer detection using PI-RADS V1 and V2 is dependent on the reader's experience. The results from the two observers indicate that structured reporting using PI-RADS and, controlled by histopathology, can be a valuable and quantifiable tool in students' or residents' education. Herein, V2 was superior to V1 in terms of inter-observer agreement and time efficacy. ADVANCES IN KNOWLEDGE: Structured reporting can be a valuable and quantifiable tool in radiologic education. Structured reporting using PI-RADS can be used by a student with good performance. PI-RADS V2 is superior to V1 in terms of inter-observer agreement and time efficacy.

Coronary computed tomography angiography and endocardial leads - Image quality in 320-row CT using iterative reconstruction.

PURPOSE: To investigate whether the presence of endocardial leads has an impact on image quality in coronary computed tomography angiography (CCTA), when current technique is employed using a 320-row computed tomography and iterative reconstruction. MATERIALS AND METHODS: CCTA was performed in 1641 patients, from these we identified 51 patients (study group) with endocardial leads and 51 matched partners (control group) without endocardial leads. Noise was determined in the ascending aorta and the left ventricle; signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were determined in the left and right coronary artery. Subjective image quality was rated separately for the 15 segments of the coronary arteries by 2 radiologists. RESULTS: Current CCTA technique still shows slight impairment of objective image quality in patients with endocardial leads with inferior SNR in the aorta (median 15.04 versus 16.6; p = 0.004) and inferior SNR in the left/right coronary artery (median 15.3/13.81 versus 16.1/15.41; p = 0.013/0.002). CNR of the left/right coronary artery was also inferior (median 17.4/16.46 versus 19.26/19.24; p = 0.002/<0.001). The subjective image quality was rated significantly inferior only in segment 8 (p = 0.001) compared to the control group. Artifacts by ventricular leads were found in 65% of the patients in segment 8 with non-diagnostic rating in 9 cases (18%). Atrial leads resulted in artifacts predominantly in segment 1 (45%) with non-diagnostic rating in only 2 cases (4%). CONCLUSION: CCTA is feasible with slight restrictions for patients in the presence of implanted cardiac devices when current technique is used.

Assessment of Systemic Adenosine Effect Using Color Doppler Ultrasound of the Splenic Artery-Feasibility and Potential Clinical Utility for Coronary Interventions.

Adenosine induces coronary vasodilation and simultaneously reduces splanchnic perfusion. This effect can be absent in adenosine non-responders. Imaging of splanchnic arteries under adenosine assessing this effect has not been performed in humans previously. In 26 patients, splenic artery color Doppler was performed during an infusion of adenosine. Peak velocity in the splenic artery was measured before the infusion and at 2 min. Results were compared qualitatively with perfusion imaging in magnetic resonance. A total of 24 patients showed a drop of splenic artery peak velocity from 62.3 ± 18.1 to 40.4 ± 15.7 cm/s (p <0.001), which corresponded to perfusion restriction in magnetic resonance. Two patients with constant splenic artery velocity did not show perfusion restriction. We showed feasibility of assessing changes in splenic artery velocity under adenosine for the first time in humans. Further studies are needed to investigate whether this novel application is a robust tool to rule out inadequate adenosine effect during measurement of fractional flow reserve in coronary catheterization.

Safety and efficacy of clip-based vs. suture mediated vascular closure for femoral access hemostasis: A prospective randomized single center study comparing the StarClose and the ProGlide device.

OBJECTIVES: This study is the first head-to-head analysis of StarClose vs. ProGlide in patients undergoing 5F or 6F percutaneous coronary catheterization or peripheral artery interventions. BACKGROUND: The clip based StarClose and the suture mediated ProGlide vascular closure device are well established for femoral hemostasis in endovascular therapy. However, until now no prospective randomized study compared the safety and efficacy of the two devices. METHODS: This prospective, randomized, single-center study enrolled 505 patients (69.6 ± 11.2 years) resulting in 538 procedures due to more than one intervention in several patients: We analyzed 422 cardiac catheterization and 116 peripheral artery interventions via a common femoral artery access. Patients were randomized to StarClose or ProGlide (1:1). In-hospital complications (major bleeding, hematoma, pseudoaneurysm, vessel occlusion, and arteriovenous fistula) and device failure were recorded. The puncture site was assessed by ultrasound in all patients prior to discharge. RESULTS: Overall complication rate was 3.9%. There were more complications after utilization of StarClose compared to ProGlide (5.6 vs. 2.2%, P = 0.064), which was significant in adjusted logistic regression analysis with a 2.9-fold increased risk of complications for StarClose (P < 0.05). In the subgroup of coronary catheterizations there were significantly more complications for StarClose compared to ProGlide (1.4 vs. 5.2%, P < 0.05) with a 4.7-fold increased risk. Device failure rate was not significantly different between the two devices. CONCLUSION: In this first randomized trial comparing the two closure systems complication rate was higher for StarClose with equal efficacy compared to ProGlide. © 2017 Wiley Periodicals, Inc.

Deactivation vs. asynchronous pacing - prospective evaluation of a protocol for rhythm management in patients with magnetic resonance conditional pacemakers undergoing adenosine stress cardiovascular magnetic resonance imaging.

BACKGROUND: Cardiovascular Magnetic Resonance (CMR) imaging with adenosine stress is an important diagnostic tool in patients with known or suspected coronary artery disease (CAD). However, the method is not yet established for CAD patients with pacemakers (PM) in clinical practice. A possible reason is that no recommendations exist for PM setting (paused pacing or asynchronous mode) during adenosine stress. We elaborated a protocol for rhythm management in clinical routine for PM patients that considers heart rate changes under adenosine using a test infusion of adenosine in selected patients. METHODS: 47 consecutive patients (mean age 72.3 ± 10,0 years) with MR conditional PM and known or suspected CAD who underwent CMR in clinical routine were studied in this prospective observational study. PM indications were sinus node dysfunction (SND, n = 19; 40,4%), atrioventricular (AV) block (n = 26; 55.3%) and bradyarrhythmia in permanent atrial fibrillation (AF, n = 2; 4.3%). In patients with SND, normal AV-conduction and resting HR >45 bpm at the time of CMR and in AF the PM was deactivated for the scan. In intermittent AV-block a test infusion of adenosine was given prior to the scan. All patients with permanent higher degree sinuatrial or AV-block or deterioration of AV-conduction in the adenosine test were paced asynchronously during CMR, in patients with preserved AV-conduction under adenosine the pacemaker was deactivated. CMR protocol included cine imaging, adenosine stress perfusion and late gadolinium enhancement. RESULTS: The adenosine test was able to differentiate between mandatory PM stimulation during CMR and safe deactivation of the device. In patients with permanent sinuatrial or AV-block (n = 11; 23.4%) or deterioration of AV conduction in the adenosine test (n = 5, 10.6%) asynchronous pacing above resting heart rate did not interfere with intrinsic rhythm, no competitive stimulation was seen during the scan. 10 of 15 (66,7%) patients with intermittent AV-block showed preserved AV-conduction under adenosine. As in SND and AF deactivation of the PM showed to be safe during CMR, no bradycardia was observed. CONCLUSION: Our protocol for rhythm management during adenosine stress CMR showed to be feasible and safe and may be recommended for pacemaker patients undergoing routine CMR.

Cardiovascular magnetic resonance in patients with magnetic resonance conditional pacemaker systems at 1.5 T: influence of pacemaker related artifacts on image quality including first pass perfusion, aortic and mitral valve assessment, flow measurement, short tau inversion recovery and T1-weighted imaging.

There are only limited data on the impact of device-related artifacts on image quality in cardiovascular magnetic resonance imaging (CMR) in patients with pacemakers (PM). Adenosine stress perfusion, T1-weighted imaging and flow measurement as well as valve characterization have not been evaluated previously concerning artifact burden. We aimed to assess image quality in all routinely used CMR sequences. We analyzed 2623 myocardial segments in CMR scans of 61 patients with MR conditional PM (mean age 72.1 ± 11.5 years), 23 (37.7%) with right sided, 38 (62.3%) with left-sided devices. There were no relevant artifacts in patients with right-sided devices irrespective of the imaging sequence. In left-sided implants no PM-induced artifacts were found in first pass perfusion sequence, flow analysis and T1 weighted imaging. Only few patients with left-sided devices showed significant PM-artifacts in aortic (3/38, 7.9%)/mitral (n = 2/38, 5.3%) valve imaging and STIR (n = 3/35, 8.6%). In STIR only 14/805 (1.7%) segments were involved. In left-sided PM SSFP cine sequences had more artifact burden than LGE with 377/1505 (25.0%) vs. 162/1505 (10.8%) myocardial segments involved by relevant artifacts respectively (p < 0.001). Apart from cine and LGE imaging in anterior myocardial segments with left-sided implants presence of MRI conditional pacemakers does not affect CMR image quality in multimodal CMR examinations to a significant extent. Our data supports evidence that reduced image quality does not need to be a major concern in PM patients undergoing CMR.

A novel cross-sector telemedical approach to detect arrhythmia in primary care patients with palpitations using a patient-activated event recorder.

BACKGROUND: Patient-activated event recorders (ER) can facilitate diagnosis in unclear palpi-tations, however impact of ER screening on further treatment in clinical routine is unknown. We investigated the feasibility and clinical value of a network-based telemetric monitoring using a patient activated ER. METHODS: The network consisted of 12 general practitioners (GP) and a department of car-diology (DC). GP-patients sent electrocardiograms (ECGs) twice daily and in case of palpitations. ECGs were transferred by email to GP and DC and analyzed independently by both. The therapeutic strategy was discussed between GP and DC. The monitoring period ended after 4 weeks or in case of detected arrhythmia. RESULTS: A group of 184 consecutive patients were retrospectively analyzed. Mean age was 57.5 ± 14.4 years (range 17-82), 104 (56.5%) were female. Significant arrhythmia occurred in 71 (38.5%) patients: Recurrence of known paroxysmal atrial fibrillation (AF; n = 27, 14.7%), de novo AF (n = 19, 10.3%), premature complexes/bigeminus (n = 13, 7.1%), sinus tachycar-dia (n = 7, 3.8%), atrioventricular nodal reentrant tachycardia (n = 3, 1.6%), and ventricular tachycardia (n = 2, 1.1%). A therapeutic consequence resulted in 63 (88.7%) patients with de-tected arrhythmia: new oral anticoagulation (n = 29, 40.8%), new antiarrhythmic medication (n = 27, 38.0%), behavioral intervention (n = 19, 26.8%), electrophysiology-study/catheter ablation (n = 4, 5.6%), cardioversion (n = 2, 2.8%), implantable cardioverter-defibrillator- -implantation (n = 1, 1.4%), and left atrial appendage occluder (n = 1, 1.4%). CONCLUSIONS: The investigated cross-sector telemetric network is a feasible approach to detect arrhythmia in patients with palpitations and may have high impact on further treatment, notably in those at risk for stroke due to AF.

Feasibility and safety of adenosine cardiovascular magnetic resonance in patients with MR conditional pacemaker systems at 1.5 Tesla.

BACKGROUND: Cardiovascular Magnetic Resonance (CMR) with adenosine stress is a valuable diagnostic tool in coronary artery disease (CAD). However, despite the development of MR conditional pacemakers CMR is not yet established in clinical routine for pacemaker patients with known or suspected CAD. A possible reason is that adenosine stress perfusion for ischemia detection in CMR has not been studied in patients with cardiac conduction disease requiring pacemaker therapy. Other than under resting conditions it is unclear whether MR safe pacing modes (paused pacing or asynchronous mode) can be applied safely because the effect of adenosine on heart rate is not precisely known in this entity of patients. We investigate for the first time feasibility and safety of adenosine stress CMR in pacemaker patients in clinical routine and evaluate a pacing protocol that considers heart rate changes under adenosine. METHODS: We retrospectively analyzed CMR scans of 24 consecutive patients with MR conditional pacemakers (mean age 72.1 ± 11.0 years) who underwent CMR in clinical routine for the evaluation of known or suspected CAD. MR protocol included cine imaging, adenosine stress perfusion and late gadolinium enhancement. RESULTS: Pacemaker indications were sinus node dysfunction (n = 18) and second or third degree AV block (n = 6). Under a pacing protocol intended to avoid competitive pacing on the one hand and bradycardia due to AV block on the other no arrhythmia occurred. Pacemaker stimulation was paused to prevent competitive pacing in sinus node dysfunction with resting heart rate >45 bpm. Sympatho-excitatory effect of adenosine led to a significant acceleration of heart rate by 12.3 ± 8.3 bpm (p < 0.001), no bradycardia occurred. On the contrary in AV block heart rate remained constant; asynchronous pacing above resting heart rate did not interfere with intrinsic rhythm. CONCLUSION: Adenosine stress CMR appears to be feasible and safe in patients with MR conditional pacemakers. Heart rate response to adenosine has to be considered for the choice of pacing modes during CMR.

Reproducibility of brain metabolite concentration measurements in lesion free white matter at 1.5 T.

BACKGROUND: Post processing for brain spectra has a great influence on the fit quality of individual spectra, as well as on the reproducibility of results from comparable spectra. This investigation used pairs of spectra, identical in system parameters, position and time assumed to differ only in noise. The metabolite amplitudes of fitted time domain spectroscopic data were tested on reproducibility for the main brain metabolites. METHODS: Proton spectra of white matter brain tissue were acquired with a short spin echo time of 30 ms and a moderate repetition time of 1500 ms at 1.5 T. The pairs were investigated with one time domain post-processing algorithm using different parameters. The number of metabolites, the use of prior knowledge, base line parameters and common or individual damping were varied to evaluate the best reproducibility. RESULTS: The protocols with most reproducible amplitudes for N-acetylaspartate, creatine, choline, myo-inositol and the combined Glx line of glutamate and glutamine in lesion free white matter have the following common features: common damping of the main metabolites, a baseline using only the points of the first 10 ms, no additional lipid/macromolecule lines and Glx is taken as the sum of separately fitted glutamate and glutamine. This parameter set is different to the one delivering the best individual fit results. DISCUSSION: All spectra were acquired in "lesion free" (no lesion signs found in MR imaging) white matter. Spectra of brain lesions, for example tumors, can be drastically different. Thus the results are limited to lesion free brain tissue. Nevertheless the application to studies is broad, because small alterations in brain biochemistry of lesion free areas had been detected nearby tumors, in patients with multiple sclerosis, drug abuse or psychiatric disorders. CONCLUSION: Main metabolite amplitudes inside healthy brain can be quantified with a normalized root mean square deviation around 5 % using CH3 of creatine as reference. Only the reproducibility of myo-inositol is roughly twice as bad. The reproducibility should be similar using other references like internal or external water for an absolute concentration evaluation and are not influenced by relaxation corrections with literature values.

Accuracy of MRI-Targeted in-Bore Prostate Biopsy According to the Gleason Score with Postprostatectomy Histopathologic Control--a Targeted Biopsy-Only Strategy with Limited Number of Cores.

RATIONALE AND OBJECTIVES: Accuracy of ultrasound-guided biopsy and Gleason score is limited, and diagnosis of insignificant cancer with Gleason score ≤6 is frequent when extended biopsy schemes are used. We evaluated whether the magnetic resonance imaging (MRI)-targeted in-bore prostate biopsy correctly identifies the Gleason score of prostate cancer in histopathologic correlation after prostatectomy. Simultaneously a targeted concept is expected to keep down the rate of insignificant cancer. MATERIALS AND METHODS: We compared retrospectively the Gleason score of the MRI-targeted in-bore biopsy with prostatectomy specimens in 50 men with prostate cancer. Endorectal MRI included T2-weighted imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging, and spectroscopy. Lesions with a prostate imaging-reporting and data system (PI-RADS) score ≥3 were considered. Upgrading and downgrading of tumors was evaluated, and significant upgrading was defined as a shift in Gleason score from 6 to 7 or more. RESULTS: Gleason score was concordant in 66% of the patients, overall upgraded in 30% of patients, and downgraded in 4% of patients. Significant upgrading of the Gleason score from 6 to 7 occurred in eight patients; upgrading did not exceed one step in the Gleason score. After prostatectomy the Gleason score 6 was found in 20% of patients. The median number of cores obtained was 4 (range 2-6), and the median number of positive cores was 2 (range 1-4). CONCLUSIONS: In-bore MRI-targeted biopsy offers good accuracy in the Gleason score with postprostatectomy histopathologic control when compared to the literature. A limited number of cores are sufficient to achieve these results. The fraction of insignificant cancer identified by targeted only-biopsy is low. Upgrading is restricted to one step in the Gleason score. Clinicians should be aware of positive findings in MRI and the biopsy technique used when assessing prostate biopsy results.

Saline as the sole contrast agent for successful MRI-guided epidural injections.

PURPOSE: To assess the performance of sterile saline solution as the sole contrast agent for percutaneous magnetic resonance imaging (MRI)-guided epidural injections at 1.5 T. METHODS: A retrospective analysis of two different techniques of MRI-guided epidural injections was performed with either gadolinium-enhanced saline solution or sterile saline solution for documentation of the epidural location of the needle tip. T1-weighted spoiled gradient echo (FLASH) images or T2-weighted single-shot turbo spin echo (HASTE) images visualized the test injectants. Methods were compared by technical success rate, image quality, table time, and rate of complications. RESULTS: 105 MRI-guided epidural injections (12 of 105 with gadolinium-enhanced saline solution and 93 of 105 with sterile saline solution) were performed successfully and without complications. Visualization of sterile saline solution and gadolinium-enhanced saline solution was sufficient, good, or excellent in all 105 interventions. For either test injectant, quantitative image analysis demonstrated comparable high contrast-to-noise ratios of test injectants to adjacent body substances with reliable statistical significance levels (p < 0.001). The mean table time was 22 ± 9 min in the gadolinium-enhanced saline solution group and 22 ± 8 min in the saline solution group (p = 0.75). CONCLUSION: Sterile saline is suitable as the sole contrast agent for successful and safe percutaneous MRI-guided epidural drug delivery at 1.5 T.

Magnetic resonance-guided interventions of large and small joints.

Magnetic resonance (MR)-guided interventions of large and small joints are feasible and safe procedures offering several advantages compared with standard guiding techniques. Nevertheless, MR-guided interventions are not routinely performed in daily practice apart from a few centers. Accurate injections are crucial for clinical outcome in diagnostic arthrography as well as therapeutic joint injections. In particular, palpatory joint puncture was shown to be inaccurate or uncertain in a substantial percentage of injections of the shoulder, the hip, and the knee. Magnetic resonance imaging offers respective merits of a cross-sectional technique with high soft-tissue contrast. Exact depiction of structures, which should be preserved, such as the labrum, should be aimed for. Areas with complex anatomy can be approached by adapting the right imaging plane(s) because of multiplanar capacity. Lack of ionizing radiation for patients is of growing interest particularly in young patients with repeated interventions. Magnetic resonance guidance alone allows an "all-in-one" MR arthrography combining precise targeting with high-field-strength imaging. Modern short-bore and open-bore high-field-strength systems offer a good comfort for patients as well as clinicians and enhance patient positioning options such as supine or prone position. Thus, a tailored approach such as a posterior technique for suspected anterior lesions in shoulder MR arthrography is possible.In this article, we describe the advantages and limitations of MR guidance in joint interventions with focus on shoulder and hip interventions. We review the requirements for needle material and MR sequences, discuss several different techniques developed to date, and present current results in clinical outcome.