Translating principles of quality control to cardiovascular magnetic resonance: assessing quantitative parameters of the left ventricle in a large cohort.

Cardiac magnetic resonance (CMR) examinations require standardization to achieve reproducible results. Therefore, quality control as known as in other industries such as in-vitro diagnostics, could be of essential value. One such method is the statistical detection of long-time drifts of clinically relevant measurements. Starting in 2010, reports from all CMR examinations of a high-volume center were stored in a hospital information system. Quantitative parameters of the left ventricle were analyzed over time with moving averages of different window sizes. Influencing factors on the acquisition and on the downstream analysis were captured. 26,902 patient examinations were exported from the clinical information system. The moving median was compared to predefined tolerance ranges, which revealed an overall of 50 potential quality relevant changes ("alerts") in SV, EDV and LVM. Potential causes such as change of staff, scanner relocation and software changes were found not to be causal of the alerts. No other influencing factors were identified retrospectively. Statistical quality assurance systems based on moving average control charts may provide an important step towards reliability of quantitative CMR. A prospective evaluation is needed for the effective root cause analysis of quality relevant alerts.

Early myocardial oedema can predict subsequent cardiomyopathy in high-dose anthracycline therapy.

AIMS: This study aims to assess subclinical changes in functional and morphologic myocardial MR parameters very early into a repetitive high-dose anthracycline treatment (planned cumulative dose >650 mg/m2 ), which may predict subsequent development of anthracycline-induced cardiomyopathy (aCMP). METHODS: Thirty sarcoma patients with previous exposition of 300-360 mg/m2 doxorubicin-equivalent chemotherapy who were planned for a second treatment of anthracycline-based chemotherapy (360 mg/m2 doxorubicin-equivalent) were recruited. Enrolled individuals received three CMR studies (before treatment, 48 h after first anthracycline treatment and upon completion of treatment). Native T1 mapping (MOLLI 5s(3s)3s), T2 mapping, and extracellular volume (ECV) maps were acquired in addition to a conventional CMR with SSFP-cine imaging at 1.5 T. Patients were given 0.2 mmol/kg gadoteridol for ECV quantification and LGE imaging. Blood samples for cardiac biomarkers were obtained before each scan. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10% compared with baseline. RESULTS: Twenty-three complete datasets were available for analysis. Median treatment time was 20.7 ± 3.0 weeks. Eight patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. Patients with aCMP had decreased LV mass upon completion of therapy (99.4 ± 26.5 g vs. 90.3 ± 24.8 g; P = 0.02), whereas patients without aCMP did not show a change in LV mass (91.5 ± 20.0 g vs. 89.0 ± 23.6 g; P > 0.05). On strain analysis, GLS (-15.3 ± 1.3 vs. -13.4 ± 1.6; P = 0.02) and GCS (-16.7 ± 2.1 vs. -14.9 ± 2.6; P = 0.04) were decreased in aCMP patients upon completion of therapy, whereas non-aCMP individuals showed no change in GLS (-15.4 ± 3.3 vs. -15.4 ± 3.4; P = 0.97). When assessed 48 h after first dose of anthracyclines, patients with subsequent aCMP had significantly elevated myocardial T2 times compared with before therapy (53.0 ± 2.8 ms vs. 49.3 ± 5.2 ms, P = 0.02) than patients who did not develop aCMP (50.7 ± 5.1 ms vs. 51.1 ± 3.9 ms, P > 0.05). Native T1 times decreased at 48 h after first dose irrespective of development of subsequent aCMP (1020.2 ± 28.4 ms vs. 973.5 ± 40.3 ms). Upon completion of therapy, patients with aCMP had increased native T1 compared with baseline (1050.8 ± 17.9 ms vs. 1022.4 ± 22.0 ms; P = 0.01), whereas non-aCMP patients did not (1034.5 ± 46.6 ms vs. 1018.4 ± 29.7 ms; P = 0.15). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy. Cardiac biomarkers were elevated independent of development of aCMP. CONCLUSIONS: With high cumulative anthracycline doses, early increase of T2 times 48 h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy. Early drop of native T1 times occurs irrespective of development of aCMP in high-dose anthracycline therapy.

Fast acquisition of left and right ventricular function parameters applying cardiovascular magnetic resonance in clinical routine - validation of a 2-shot compressed sensing cine sequence.

Objectives. To evaluate if cine sequences accelerated by compressed sensing (CS) are feasible in clinical routine and yield equivalent cardiac morphology in less time. Design. We evaluated 155 consecutive patients with various cardiac diseases scanned during our clinical routine. LV and RV short axis (SAX) cine images were acquired by conventional and prototype 2-shot CS sequences on a 1.5 T CMR. The 2-shot prototype captures the entire heart over a period of 3 beats making the acquisition potentially even faster. Both scans were performed with identical slice parameters and positions. We compared LV and RV morphology with Bland-Altmann plots and weighted the results in relation to pre-defined tolerance intervals. Subjective and objective image quality was evaluated using a 4-point score and adapted standardized criteria. Scan times were evaluated for each sequence. Results. In total, no acquisitions were lost due to non-diagnostic image quality in the subjective image score. Objective image quality analysis showed no statistically significant differences. The scan time of the CS cines was significantly shorter (p < .001) with mean scan times of 178 ± 36 s compared to 313 ± 65 s for the conventional cine. All cardiac function parameters showed excellent correlation (r 0.978-0.996). Both sequences were considered equivalent for the assessment of LV and RV morphology. Conclusions. The 2-shot CS SAX cines can be used in clinical routine to acquire cardiac morphology in less time compared to the conventional method, with no total loss of acquisitions due to nondiagnostic quality. TRIAL REGISTRATION: ISRCTN12344380. Registered 20 November 2020, retrospectively registered.

Z-score mapping for standardized analysis and reporting of cardiovascular magnetic resonance modified Look-Locker inversion recovery (MOLLI) T1 data: Normal behavior and validation in patients with amyloidosis.

BACKGROUND: T1 mapping using modified Look-Locker inversion recovery (MOLLI) provides quantitative information on myocardial tissue composition. T1 results differ between sites due to variations in hardware and software equipment, limiting the comparability of results. The aim was to test if Z-scores can be used to compare the results of MOLLI T1 mapping from different cardiovascular magnetic resonance (CMR) platforms. METHODS: First, healthy subjects (n = 15) underwent 11 combinations of native short-axis T1 mapping (four CMR systems from two manufacturers at 1.5 T and 3 T, three MOLLI schemes). Mean and standard deviation (SD) of septal myocardial T1 were derived for each combination. T1 maps were transformed into Z-score maps based on mean and SD values using a prototype post-processing module. Second, Z-score mapping was applied to a validation sample of patients with cardiac amyloidosis at 1.5 T (n = 25) or 3 T (n = 13). RESULTS: In conventional T1 analysis, results were confounded by variations in field strength, MOLLI scheme, and manufacturer-specific system characteristics. Z-score-based analysis yielded consistent results without significant differences between any two of the combinations in part 1 of the study. In the validation sample, Z-score mapping differentiated between patients with cardiac amyloidosis and healthy subjects with the same diagnostic accuracy as standard T1 analysis regardless of field strength. CONCLUSIONS: T1 analysis based on Z-score mapping provides consistent results without significant differences due to field strengths, CMR systems, or MOLLI variants, and detects cardiac amyloidosis with the same diagnostic accuracy as conventional T1 analysis. Z-score mapping provides a means to compare native T1 results acquired with MOLLI across different CMR platforms.

Cardiac 123I-MIBG Scintigraphy in Neurodegenerative Parkinson Syndromes: Performance and Pitfalls in Clinical Practice.

Purpose: Cardiac [123I]metaiodobenzylguanidine scintigraphy (123I-MIBG), reflecting postganglionic cardiac autonomic denervation, is proposed for early detection of Parkinson's disease (PD; reduced tracer uptake) and separation from Multiple System Atrophy (MSA; preserved tracer uptake). However, several recent studies report on frequent unexpected 123I-MIBG results in PD and MSA. We sought to determine, whether 123I-MIBG is feasible to discriminate PD from MSA in unselected geriatric patients in clinical practice. Materials and Methods: We screened consecutive patients, that underwent 123I-MIBG for diagnostic reasons. Delayed 123I-MIBG uptake (heart/mediastinum ratio; H/M ratio) was verified by clinical diagnosis of PD, MSA, and ET based on a two-stage clinical assessment: comprehensive baseline (including autonomic testing and additional neuroimaging) and confirmatory clinical follow-up. Results: 28 patients with clinical diagnosis of PD (N = 11), MSA (N = 9), and Essential Tremor (ET, N = 8) were identified. In one third (9/28) nuclear medical diagnosis deviated from clinically suspected syndrome. Visual interpretation of 123I-MIBG identified two cases (MSA and ET) with indeed normal 123I-MIBG uptake. Detailed review of clinical phenotypes provided only in two cases (PD and ET) an adequate explanation (correction of initial diagnosis and confounding drug history) for unexpected 123I-MIBG. In conclusion, 123I-MIBG did not match initial clinical phenotype in 27% PD, 44% MSA, and 25% ET patients. Conclusion: 123I-MIBG scintigraphy is a known specific and valuable technique in scientific approaches and well-defined and highly selected samples. However, predictability of 123I-MIBG based nuclear medical diagnosis for individual cases and thus, feasibility in routine clinical practice is limited. Our clinical series emphasize clinical verification of 123I-MIBG results on an individual basis in clinical routine.

Quantification in cardiovascular magnetic resonance: agreement of software from three different vendors on assessment of left ventricular function, 2D flow and parametric mapping.

BACKGROUND: Quantitative results of cardiovascular magnetic resonance (CMR) image analysis influence clinical decision making. Image analysis is performed based on dedicated software. The manufacturers provide different analysis tools whose algorithms are often unknown. The aim of this study was to evaluate the impact of software on quantification of left ventricular (LV) assessment, 2D flow measurement and T1- and T2-parametric mapping. METHODS: Thirty-one data sets of patients who underwent a CMR Scan on 1.5 T were analyzed using three different software (Circle CVI: cvi42, Siemens Healthineers: Argus, Medis: Qmass/Qflow) by one reader blinded to former results. Cine steady state free precession short axis images were analyzed regarding LV ejection fraction (EF), end-systolic and end-diastolic volume (ESV, EDV) and LV mass. Phase-contrast magnetic resonance images were evaluated for forward stroke volume (SV) and peak velocity (Vmax). Pixel-wise generated native T1- and T2-maps were used to assess T1- and T2-time. Forty-five data sets were evaluated twice (15 per software) for intraobserver analysis. Equivalence was considered if the confidence interval of a paired assessment of two sofware was within a tolerance interval defined by ±1.96 highest standard deviation obtained by intraobserver analysis. RESULTS: For each parameter, thirty data sets could be analyzed with all three software. All three software (A/B, A/C, B/C) were considered equivalent for LV EF, EDV, ESV, mass, 2D flow SV and T2-time. Differences between software were detected in flow measurement for Vmax and in parametric mapping for T1-time. For Vmax, equivalence was given between software A and C and for T1-time equivalence was given between software B and C. CONCLUSION: Software had no impact on quantitative results of LV assessment, T2-time and SV based on 2D flow. In contrast to that, Vmax and T1-time may be influenced by software. CMR reports should contain the name and version of the software applied for image analysis to avoid misinterpretation upon follow-up and research examinations. TRIAL REGISTRATION: ISRCTN12210850 . Registered 14 July 2017, retrospectively registered.

Native myocardial T1 time can predict development of subsequent anthracycline-induced cardiomyopathy.

AIMS: This study aims to assess subclinical changes in functional and morphological myocardial magnetic resonance parameters very early into an anthracycline treatment, which may predict subsequent development of anthracycline-induced cardiomyopathy (aCMP). METHODS AND RESULTS: Thirty sarcoma patients with planned anthracycline-based chemotherapy (360-400 mg/m2 doxorubicin-equivalent) were recruited. Median treatment time was 19.1 ± 2.1 weeks. Enrolled individuals received three cardiovascular magnetic resonance studies (before treatment, 48 h after first anthracycline treatment, and upon completion of treatment). Native T1 mapping (modified Look-Locker inversion recovery 5s(3s)3s), T2 mapping, and extracellular volume maps were acquired in addition to a conventional cardiovascular magnetic resonance with steady-state free precession cine imaging at 1.5 T. Patients were given 0.2 mmol/kg gadoteridol for extracellular volume quantification and late gadolinium enhancement imaging. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10%. For analysis, 23 complete data sets were available. Nine patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. When assessed 48 h after first dose of antracyclines, patients with subsequent aCMP had significantly lower native myocardial T1 times compared with before therapy (1002.0 ± 37.9 vs. 956.5 ± 29.2 ms, P < 0.01) than patients who did not develop aCMP (990.9 ± 56.4 vs. 978.4 ± 57.4 ms, P > 0.05). Patients with aCMP had decreased left ventricular mass upon completion of therapy (86.9 ± 24.5 vs. 81.1 ± 22.3 g; P = 0.02), while patients without aCMP did not show a change in left ventricular mass (81.8 ± 21.0 vs. 79.2 ± 18.1 g; P > 0.05). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy. CONCLUSIONS: Early decrease of T1 times 48 h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy.

Comparison of fast multi-slice and standard segmented techniques for detection of late gadolinium enhancement in ischemic and non-ischemic cardiomyopathy - a prospective clinical cardiovascular magnetic resonance trial.

BACKGROUND: Segmented phase-sensitive inversion recovery (PSIR) cardiovascular magnetic resonance (CMR) sequences are reference standard for non-invasive evaluation of myocardial fibrosis using late gadolinium enhancement (LGE). Several multi-slice LGE sequences have been introduced for faster acquisition in patients with arrhythmia and insufficient breathhold capability. The aim of this study was to assess the accuracy of several multi-slice LGE sequences to detect and quantify myocardial fibrosis in patients with ischemic and non-ischemic myocardial disease. METHODS: Patients with known or suspected LGE due to chronic infarction, inflammatory myocardial disease and hypertrophic cardiomyopathy (HCM) were prospectively recruited. LGE images were acquired 10-20 min after administration of 0.2 mmol/kg gadolinium-based contrast agent. Three different LGE sequences were acquired: a segmented, single-slice/single-breath-hold fast low angle shot PSIR sequence (FLASH-PSIR), a multi-slice balanced steady-state free precession inversion recovery sequence (bSSFP-IR) and a multi-slice bSSFP-PSIR sequence during breathhold and free breathing. Image quality was evaluated with a 4-point scoring system. Contrast-to-noise ratios (CNR) and acquisition time were evaluated. LGE was quantitatively assessed using a semi-automated threshold method. Differences in size of fibrosis were analyzed using Bland-Altman analysis. RESULTS: Three hundred twelve patients were enrolled (n = 212 chronic infarction, n = 47 inflammatory myocardial disease, n = 53 HCM) Of which 201 patients (67,4%) had detectable LGE (n = 143 with chronic infarction, n = 27 with inflammatory heart disease and n = 31 with HCM). Image quality and CNR were best on multi-slice bSSFP-PSIR. Acquisition times were significantly shorter for all multi-slice sequences (bSSFP-IR: 23.4 ± 7.2 s; bSSFP-PSIR: 21.9 ± 6.4 s) as compared to FLASH-PSIR (361.5 ± 95.33 s). There was no significant difference of mean LGE size for all sequences in all study groups (FLASH-PSIR: 8.96 ± 10.64 g; bSSFP-IR: 8.69 ± 10.75 g; bSSFP-PSIR: 9.05 ± 10.84 g; bSSFP-PSIR free breathing: 8.85 ± 10.71 g, p > 0.05). LGE size was not affected by arrhythmia or absence of breathhold on multi-slice LGE sequences. CONCLUSIONS: Fast multi-slice and standard segmented LGE sequences are equivalent techniques for the assessment of myocardial fibrosis, independent of an ischemic or non-ischemic etiology. Even in patients with arrhythmia and insufficient breathhold capability, multi-slice sequences yield excellent image quality at significantly reduced scan time and may be used as standard LGE approach. TRIAL REGISTRATION: ISRCTN48802295 (retrospectively registered).

Buerger's disease: providing integrated care.

Buerger's disease, also known as thromboangiitis obliterans (TAO), is a segmental inflammatory disease affecting small- and medium-sized vessels, which is strongly associated with tobacco use. Although the etiology is still unknown, recent studies suggest an immunopathogenesis. Diagnosis is based on clinical and angiomorphologic criteria, including age, history of smoking, clinical presentation with distal extremity ischemia, and the absence of other risk factors for atherosclerosis, autoimmune disease, hypercoagulable states, or embolic disease. Until now, no causative therapy exists for TAO. The most important therapeutic intervention is smoking cessations and intravenous prostanoid infusions (iloprost). Furthermore, effective analgesia is crucial for the treatment of ischemic and neuropathic pain and might be expanded by spinal cord stimulation. Revascularization procedures do not play a major role in the treatment of TAO due to the distal localization of arterial occlusion. More recently, immunoadsorption has been introduced eliminating vasoconstrictive G-protein-coupled receptor and other autoantibodies. Cell-based therapies and treatment with bosentan were also advocated. Finally, a consequent prevention and treatment of wounds and infections are essential for the prevention of amputations. To achieve better clinical results, integrated care in multidisciplinary and trans-sectoral teams with emphasis on smoking cessation, pain control, wound management, and social care by professionals, social workers, and family members is necessary.

Accuracy and repeatability of two methods of gait analysis - GaitRite™ und Mobility Lab™ - in subjects with cerebellar ataxia.

Instrumental gait analysis is increasingly recognized as a useful tool for the evaluation of movement disorders. The various assessment devices available to date have mostly been evaluated in healthy populations only. We aimed to explore whether reliability and validity seen in healthy subjects can also be assumed in subjects with cerebellar ataxic gait. Gait was recorded simultaneously with two devices - a sensor-embedded walkway and an inertial sensor based system - to explore test accuracy in two groups of subjects: one with mild to moderate cerebellar ataxia due to a subtype of autosomal-dominantly inherited neurodegenerative disorder (SCA14), the other were healthy subjects matched for age and height (CTR). Test precision was assessed by retest within session for each device. In conclusion, accuracy and repeatability of gait measurements were not compromised by ataxic gait disorder. The accuracy of spatial measures was speed-dependent and a direct comparison of stride length from both devices will be most reliably made at comfortable speed. Measures of stride variability had low agreement between methods in CTR and at retest in both groups. However, the marked increase of stride variability in ataxia outweighs the observed amount of imprecision.

Phosphorylated α-synuclein in skin nerve fibres differentiates Parkinson's disease from multiple system atrophy.

Deposition of phosphorylated SNCA (also known as α-synuclein) in cutaneous nerve fibres has been shown pre- and post-mortem in Parkinson's disease. Thus far, no pre-mortem studies investigating the presence of phosphorylated SNCA in skin sympathetic nerve fibres of multiple system atrophy, another synucleinopathy, have been conducted. In this in vivo study, skin from the ventral forearm of 10 patients with multiple system atrophy and 10 with Parkinson's disease, together with six control subjects with essential tremor, were examined by immunohistochemistry. Phosphorylated SNCA deposits in skin sympathetic nerve fibres and dermal nerve fibre density were assessed. All patients with Parkinson's disease expressed phosphorylated SNCA in sympathetic skin nerve fibres, correlating with an age-independent denervation of autonomic skin elements. In contrast, no phosphorylated SNCA was found in autonomic skin nerve fibres of patients with multiple system atrophy and essential tremor control subjects. These findings support that phosphorylated SNCA deposition is causative for nerve fibre degeneration in Parkinson's disease. Moreover, pre-mortem investigation of phosphorylated SNCA in cutaneous nerve fibres may prove a relevant and easily conductible diagnostic procedure to differentiate Parkinson's disease from multiple system atrophy.