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Acute allograft injury was observed in a 37-year-old woman within a few weeks after kidney transplantation. Neither renal ultrasound nor computerized tomography (CT) and magnetic resonance (MR) angiography revealed any anomaly. An MR protocol was then performed including arterial spin labeling and intravoxel incoherent motion diffusion weighted imaging. Both arterial spin labeling and the perfusion fraction in the diffusion weighted imaging showed decreased perfusion compared to reference values. The patient subsequently underwent angiography, where an arteriovenous fistula in the upper calix of the transplant kidney was detected and immediate embolization was performed. A second functional MR, performed one week later, demonstrated a 40% increase in organ perfusion. We conclude that functional MR with arterial spin labeling and intravoxel incoherent motion have the potential to provide complementary information of clinical value to conventional imaging for monitoring renal allografts.

Background: Static [18F]FDG-PET/CT is the imaging method of choice for the evaluation of indeterminate lung lesions and NSCLC staging; however, histological confirmation of PET-positive lesions is needed in most cases due to its limited specificity. Therefore, we aimed to evaluate the diagnostic performance of additional dynamic whole-body PET. Methods: A total of 34 consecutive patients with indeterminate pulmonary lesions were enrolled in this prospective trial. All patients underwent static (60 min p.i.) and dynamic (0–60 min p.i.) whole-body [18F]FDG-PET/CT (300 MBq) using the multi-bed-multi-timepoint technique (Siemens mCT FlowMotion). Histology and follow-up served as ground truth. Kinetic modeling factors were calculated using a two-compartment linear Patlak model (FDG influx rate constant = Ki, metabolic rate = MR-FDG, distribution volume = DV-FDG) and compared to SUV using ROC analysis. Results: MR-FDGmean provided the best discriminatory power between benign and malignant lung lesions with an AUC of 0.887. The AUC of DV-FDGmean (0.818) and SUVmean (0.827) was non-significantly lower. For LNM, the AUCs for MR-FDGmean (0.987) and SUVmean (0.993) were comparable. Moreover, the DV-FDGmean in liver metastases was three times higher than in bone or lung metastases. Conclusions: Metabolic rate quantification was shown to be a reliable method to detect malignant lung tumors, LNM, and distant metastases at least as accurately as the established SUV or dual-time-point PET scans.

Background Patients with locally-advanced non-small-cell lung cancer (LA-NSCLC) are often ineligible for surgery, so that definitive chemoradiotherapy (CRT) represents the treatment of choice. Nevertheless, long-term tumor control is often not achieved. Intensification of radiotherapy (RT) to improve locoregional tumor control is limited by the detrimental effect of higher radiation exposure of thoracic organs-at-risk (OAR). This narrow therapeutic ratio may be expanded by exploiting the advantages of magnetic resonance (MR) linear accelerators, mainly the online adaptation of the treatment plan to the current anatomy based on daily acquired MR images. However, MR-guidance is both labor-intensive and increases treatment times, which raises the question of its clinical feasibility to treat LA-NSCLC. Therefore, the PUMA trial was designed as a prospective, multicenter phase I trial to demonstrate the clinical feasibility of MR-guided online adaptive RT in LA-NSCLC. Methods Thirty patients with LA-NSCLC in stage III A-C will be accrued at three German university hospitals to receive MR-guided online adaptive RT at two different MR-linac systems (MRIdian Linac®, View Ray Inc. and Elekta Unity®, Elekta AB) with concurrent chemotherapy. Conventionally fractioned RT with isotoxic dose escalation up to 70 Gy is applied. Online plan adaptation is performed once weekly or in case of major anatomical changes. Patients are followed-up by thoracic CT- and MR-imaging for 24 months after treatment. The primary endpoint is twofold: (1) successfully completed online adapted fractions, (2) on-table time. Main secondary endpoints include adaptation frequency, toxicity, local tumor control, progression-free and overall survival. Discussion PUMA aims to demonstrate the clinical feasibility of MR-guided online adaptive RT of LA-NSCLC. If successful, PUMA will be followed by a clinical phase II trial that further investigates the clinical benefits of this approach. Moreover, PUMA is part of a large multidisciplinary project to develop MR-guidance techniques. Trial registration ClinicalTrials.gov: NCT05237453.

Background Arterial spin labeling (ASL) MRI can be used to assess organ perfusion but has yet to be implemented for perfusion evaluation of the lung. Purpose To evaluate pseudo-continuous ASL (PCASL) MRI for the detection of acute pulmonary embolism (PE) and its potential as an alternative to CT pulmonary angiography (CTPA). Materials and Methods Between November 2020 and November 2021, 97 patients (median age, 61 years; 48 women) with suspected PE were enrolled in this prospective study. PCASL MRI was performed within a 72-hour period following CTPA under free-breathing conditions and included three orthogonal planes. The pulmonary trunk was labeled during systole, and the image was acquired during diastole of the subsequent cardiac cycle. Additionally, multisection, coronal, balanced, steady-state free-precession imaging was carried out. Two radiologists blindly assessed overall image quality, artifacts, and diagnostic confidence (five-point Likert scale, 5 = best). Patients were categorized as positive or negative for PE, and a lobe-wise assessment in PCASL MRI and CTPA was conducted. Sensitivity and specificity were calculated on a patient level with the final clinical diagnosis serving as the reference standard. Interchangeability between MRI and CTPA was also tested with use of an individual equivalence index (IEI). Results PCASL MRI was performed successfully in all patients with high scores for image quality, artifact, and diagnostic confidence (κ ≥ .74). Of the 97 patients, 38 were positive for PE. PCASL MRI depicted PE correctly in 35 of 38 patients with three false-positive and three false-negative findings, resulting in a sensitivity of 35 of 38 patients (92% [95% CI: 79, 98]) and a specificity of 56 of 59 patients (95% [95% CI: 86, 99]). Interchangeability analysis revealed an IEI of 2.6% (95% CI: 1.2, 3.8). Conclusion Free-breathing pseudo-continuous arterial spin labeling MRI depicted abnormal lung perfusion caused by acute pulmonary embolism and may be useful as a contrast material-free alternative to CT pulmonary angiography for selected patients. German Clinical Trials Register no. DRKS00023599

Early tumor size reduction (TSR) has been explored as a prognostic factor for survival in patients with advanced melanoma in clinical trials. The purpose of this analysis is to validate, in a routine clinical milieu, the predictive capacity of TSR by 10% for overall survival (OS) and progression-free survival (PFS) and to compare its predictive performance with the RECIST 1.1 criteria.This retrospective study was approved by the local ethics committee. A total of 152 patients with both CT before immunotherapy initiation and at first response evaluation after immunotherapy initiation were included. Prior to statistical analysis, treatment response was trichotomized as follows: Complete response and/or partial response, stable disease and progressive disease. Furthermore, response was dichotomized regarding TSR (TSR ≥ 10% and TSR10%). Kaplan-Meier survival estimates, Cox regression and Harrel's concordance index (C-index) were computed for prediction of overall survival and progression-free survival.Tumor size reduction by at least 10% significantly differentiated between patients with increased survival from the ones with decreased survival (median OS: TSR ≥ 10%: 2137 days vs. TSR10%: 263 days) (p0.001) (median PFS: TSR ≥ 10%: 590 days vs. TSR10%: 11 days) (p0.001). RECIST 1.1. criteria had a slightly higher C-index for overall survival reflecting a slight superior predictive capacity (RECIST: 0.69 vs TSR: 0.64) but a similar predictive capacity regarding progression-free survival (both: 0. 63).Early tumor size reduction serves as a simple-to-use metric which can be implemented on the first follow-up CT. Tumor size reduction by at least 10% can be considered an additional biomarker predictive of overall survival and progression-free survival in routine clinical care and not only in the context of clinical trials in patients with advanced melanoma undergoing immunotherapy. Nevertheless, RECIST-based criteria should remain the main tool of treatment response assessment until results of prospective studies validating the TSR method are available.

Background: Acute mesenteric ischemia (AMI) is a life-threatening condition resulting from occlusion of the mesenteric arterial vessels. AMI requires immediate treatment with revascularization of the occluded vessels. Purpose: to evaluate the technical success, clinical outcomes and survival of patients receiving endovascular treatment for AMI followed by surgery. Material and Methods: A search of our institution’s database for AMI revealed 149 potential patients between 08/2016 and 08/2021, of which 91 were excluded due to incomplete clinical data, insufficient imaging or missing follow-up laparoscopy. The final cohort included 58 consecutive patients [(median age 73.5 years [range: 43–96 years], 55% female), median BMI 26.2 kg/m2 (range:16.0–39.2 kg/m2)]. Periinterventional imaging regarding the cause of AMI (acute-embolic or acute-on-chronic) was evaluated by two radiologists in consensus. The extent of AMI and the degree of technical success was graded according to a modified TICI (Thrombolysis in Cerebral Infarction scale) score (TICI-AMI) classification (0: no perfusion; 1: minimal; 2a < 50% filling; 2b > 50%; 2c: near complete or slow; 3: complete). Lab data and clinical data were collected, including the results of follow-up laparoscopy. Non-parametric statistics were used. Results: All interventions were considered technically successful. The most common causes of AMI were emboli (51.7%) and acute-on-chronic thrombotic occlusions (37.9%). Initial imaging showed a TICI-AMI score of 0, 1 or 2a in 87.9% (n = 51) of patients. Post-therapeutic TICI-AMI scores improved significantly with 87.9% of patients grade 2b and better. Median lactate levels reduced from 2.7 (IQR 2.0–3.7) mg/dL (1–18) to 1.45 (IQR 0.99–1.90). Intestinal ischemia was documented in 79.1% of cases with resection of the infarcted intestinal loops. In total, 22/58 (37.9%) patients died during the first 30 days after intervention and surgery. According to CIRSE criteria, we did not observe any SAE scores of grade 2 or higher. Conclusions: AMI is a serious disease with high lethality within the first 30 days despite optimal treatment. However, interventional revascularization before surgery with resection of the infarcted bowel can save two out of three of critically ill patients.

Acute pulmonary embolism (PE) can be a life-threatening event that requires immediate care to maintain cardiovascular circulation. In addition to systemic thrombolytic therapy, mechanical thrombectomy may be indicated in cases with a high or intermediate risk of mortality, to directly remove obstructive emboli for rapid patient improvement [1]. Several devices for catheter-directed thrombolysis and mechanical thrombectomy are available, and data regarding the efficacy of these procedures are inconsistent. Non-invasive imaging of pulmonary blood flow might help evaluate treatment success and support the acceptance of revascularization procedures. Arterial spin labeling (ASL)-MRI is a well-established technique in brain imaging to measure organ perfusion without the need for contrast agents, using blood as an endogenous tracer. Perfusion imaging with ASL has already been implemented in routine clinical diagnosis of cerebrovascular pathologies, including arterio-occlusive disease, vascular shunts, and neuro-degenerative diseases [2]. In the lung, the complex vessel anatomy, highly pulsatile nature of blood flow, respiratory movements, and low proton density are challenging conditions for ASL-MRI, hindering its translation to routine clinical use. We recently presented electrocardiogram-triggered pseudo-continuous ASL (PCASL) imaging with balanced steady-state free precession readout at 1.5T as a promising approach to enable the imaging of pulmonary blood flow even under free-breathing conditions [3]. We aimed to demonstrate the first use of PCASL-MRI in patients to monitor the treatment success of catheter-directed mechanical thrombectomy. A 79-year-old female patient was brought to our emergency unit with clinical signs of PE. A contrast-enhanced CT-scan was performed showing a massive occlusion of the right and left pulmonary arteries with signs of right ventricular dysfunction (Fig. 1A-C). Right ventricular strain was diagnosed on echocardiography and electrocardiogram (Fig. 1D). In accordance with the European Society of Cardiology (ESC) guidelines and after interdisciplinary discussion, the patient was brought to the angiography suite in our radiology department for mechanical thrombectomy.

[18F]FDG PET/MRI was shown to have limited sensitivity for N-staging in FIGO I/II cervical carcinoma. Therefore, this prospective study aimed to investigate the additional value of multiparametric dual-time-point PET/MRI and to assess potential influencing factors for lymph node metastasis (LNM) detection. A total of 63 patients underwent whole-body dual-time-point [18F]FDG PET/MRI 60 + 90 min p.i., and 251 LN were evaluated visually, quantified multiparametrically, and correlated with histology. Grading of the primary tumor (G2/G3) had a significant impact on visual detection (sens: 8.3%/31%). The best single parameter for LNM detection was SUVavg, however, with a significant loss of discriminatory power in G2 vs. G3 tumors (AUC: 0.673/0.901). The independent predictors SUVavg, ∆SUVpeak, LN sphericity, ADC, and histologic grade were included in the logistic-regression-based malignancy score (MS) for multiparametric analysis. Application of MS enhanced AUCs, especially in G2 tumors (AUC: G2:0.769; G3:0.877) and improved the accuracy for single LNM from 34.5% to 55.5% compared with the best univariate parameter SUVavg. Compared with visual analysis, the use of the malignancy score increased the overall sensitivity from 31.0% to 79.3% (Youden optimum) with a moderate decrease in specificity from 98.3% to 75.6%. These findings indicate that multiparametric evaluation of dual-time-point PET/MRI has the potential to improve accuracy compared with visual interpretation and enables sufficient N-staging also in G2 cervical carcinoma.

Until today, assessment of renal function has remained a challenge for modern medicine. In many cases, kidney diseases accompanied by a decrease in renal function remain undetected and unsolved, since neither laboratory tests nor imaging diagnostics provide adequate information on kidney status. In recent years, developments in the field of functional magnetic resonance imaging with application to abdominal organs have opened new possibilities combining anatomic imaging with multiparametric functional information. The multiparametric approach enables the measurement of perfusion, diffusion, oxygenation, and tissue characterization in one examination, thus providing more comprehensive insight into pathophysiological processes of diseases as well as effects of therapeutic interventions. However, application of multiparametric fMRI in the kidneys is still restricted mainly to research areas and transfer to the clinical routine is still outstanding. One of the major challenges is the lack of a standardized protocol for acquisition and postprocessing including efficient strategies for data analysis. This article provides an overview of the most common fMRI techniques with application to the kidney together with new approaches regarding data analysis with deep learning.This article implies a selective literature review using the literature database PubMed in May 2021 supplemented by our own experiences in this field.Functional multiparametric MRI is a promising technique for assessing renal function in a more comprehensive approach by combining multiple parameters such as perfusion, diffusion, and BOLD imaging. New approaches with the application of deep learning techniques could substantially contribute to overcoming the challenge of handling the quantity of data and developing more efficient data postprocessing and analysis protocols. Thus, it can be hoped that multiparametric fMRI protocols can be sufficiently optimized to be used for routine renal examination and to assist clinicians in the diagnostics, monitoring, and treatment of kidney diseases in the future.· Multiparametric fMRI is a technique performed without the use of radiation, contrast media, and invasive methods.. · Multiparametric fMRI provides more comprehensive insight into pathophysiological processes of kidney diseases by combining functional and structural parameters.. · For broader acceptance of fMRI biomarkers, there is a need for standardization of acquisition, postprocessing, and analysis protocols as well as more prospective studies.. · Deep learning techniques could significantly contribute to an optimization of data acquisition and the postprocessing and interpretation of larger quantities of data..· Zhang C, Schwartz M, Küstner T et al. Multiparametric Functional MRI of the Kidney: Current State and Future Trends with Deep Learning Approaches. Fortschr Röntgenstr 2022; 194: 983 - 992.Bis heute stellt die Erfassung der Nierenfunktion eine Herausforderung für die moderne Medizin dar. Oftmals bleiben funktionelle Einschränkungen der Niere unentdeckt und die Ursachen ungeklärt, da weder die Labordiagnostik noch zur Verfügung stehende Bildgebungsmethoden ausreichend Information über den Funktionsstatus der Nieren liefern. In den letzten Jahren haben Entwicklungen auf dem Gebiet der multiparametrischen funktionellen Magnetresonanztomografie (fMRT) mit Anwendung an abdominellen Organen neue Möglichkeiten zur kombinierten Erfassung anatomischer Strukturen und funktioneller Informationen eröffnet. Dieser multiparametrische Ansatz erlaubt die Messung verschiedener Parameter wie der Perfusion, Diffusion, Oxygenierung und Charakterisierung von Gewebeparametern in einem Untersuchungsvorgang, wodurch umfassendere Einblicke in die pathophysiologischen Prozesse verschiedener Nierenerkrankungen und die Wirkung therapeutischer Ansätze ermöglicht werden. Allerdings ist die Anwendung an der Niere noch auf die Forschung beschränkt und der Schritt in die klinische Routinediagnostik ausstehend. Eine der größten Herausforderungen stellt das Fehlen standardisierter Protokolle für die Akquisition und die Datenverarbeitung sowie effizienter Methoden zur Datenanalyse dar. Dieses Review bietet eine Übersicht über die weitverbreitetsten fMRT-Techniken mit Anwendung an der Niere und zeigt neue Ansätze zur Datenverarbeitung und Analyse mittels Deep Learning auf.Für diesen Artikel wurde eine selektive Literaturrecherche unter Verwendung der Literaturdatenbank PubMed im Mai 2021 durchgeführt und durch eigene Erfahrungen auf diesem Gebiet ergänzt.Die multiparametrische funktionelle MRT ist eine vielversprechende Technik zur Erfassung der Nierenfunktion in einem umfassenderen Ansatz durch kombinierte Untersuchung verschiedener Funktionsparameter wie der Perfusion, Diffusion und Oxygenierung in einem Untersuchungsablauf. Neue Entwicklungen auf dem Gebiet des Deep Learning könnten wesentlich bei der Bewältigung der Datenmengen und der Entwicklung effizienterer Methoden zur Datenverarbeitung und Analyse beitragen. Diese Fortschritte lassen hoffen, dass multiparametrische fMRT-Protokolle bald ausreichend optimiert sind, um über die Forschung hinaus auch im klinischen Alltag in der Diagnostik, dem Monitoring und der Behandlung von Nierenerkrankungen eingesetzt zu werden.· Die multiparametrische fMRT umfasst strahlenfreie, nicht invasive und kontrastmittelfreie Techniken.. · Durch die kombinierte Aufnahme verschiedener funktioneller und struktureller Gewebeparameter können tiefere Einblicke in pathophysiologische Prozesse von Nierenerkrankungen gewonnen werden.. · Für eine breitere Akzeptanz von MR-Biomarkern in der Zukunft sind die Etablierung von Standards in der Datenakquisition, -verarbeitung und Analyse sowie prospektive Studien notwendig.. · Deep-Learning-Ansätze könnten einen entscheidenden Beitrag sowohl in der Datenakquisition als auch in der Verarbeitung und Interpretation großer Datenmengen leisten..

Machine learning (ML) is considered an important technology for future data analysis in health care.The inherently technology-driven fields of diagnostic radiology and nuclear medicine will both benefit from ML in terms of image acquisition and reconstruction. Within the next few years, this will lead to accelerated image acquisition, improved image quality, a reduction of motion artifacts and - for PET imaging - reduced radiation exposure and new approaches for attenuation correction. Furthermore, ML has the potential to support decision making by a combined analysis of data derived from different modalities, especially in oncology. In this context, we see great potential for ML in multiparametric hybrid imaging and the development of imaging biomarkers.In this review, we will describe the basics of ML, present approaches in hybrid imaging of MRI, CT, and PET, and discuss the specific challenges associated with it and the steps ahead to make ML a diagnostic and clinical tool in the future.· ML provides a viable clinical solution for the reconstruction, processing, and analysis of hybrid imaging obtained from MRI, CT, and PET..· Küstner T, Hepp T, Seith F. Multiparametric Oncologic Hybrid Imaging: Machine Learning Challenges and Opportunities. Fortschr Röntgenstr 2022; 194: 605 - 612.Maschinelles Lernen (ML) gilt als eine wichtige Technologie für die zukünftige Datenanalyse im Gesundheitswesen.Die inhärent technologiegetriebene diagnostische Radiologie und Nuklearmedizin werden sowohl bei der Bildaufnahme als auch bei der Bildrekonstruktion von ML profitieren. In den nächsten Jahren wird dies zu einer beschleunigten Bildaufnahme, einer verbesserten Bildqualität, einer Reduzierung von Bewegungsartefakten und – für die PET-Bildgebung – zu einer reduzierten Strahlenexposition und neuen Ansätzen zur Schwächungskorrektur führen. Darüber hinaus hat ML das Potenzial, die Entscheidungsfindung durch eine kombinierte Analyse von Daten aus verschiedenen Modalitäten, insbesondere im Bereich der Onkologie, zu unterstützen. In diesem Zusammenhang sehen wir ein großes Potenzial für ML in der multiparametrischen Hybrid-Bildgebung und der Entwicklung von bildgebenden Biomarkern.In diesem Review werden wir die Grundlagen von ML beschreiben, Ansätze in der hybriden Bildgebung von MRT, CT und PET vorstellen und die damit verbundenen spezifischen Herausforderungen und die kommenden Schritte diskutieren, um ML in Zukunft zu einem diagnostischen und klinischen Werkzeug zu machen.· ML bietet eine praktikable klinische Lösung für die Rekonstruktion, Verarbeitung und Analyse von Hybrid-Bildgebung der MRT, CT und PET..

Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. An important gatekeeper for the therapeutic response to ICT are CD8+ cytotoxic T cells which are able to recognize MHC class I-dependent tumor antigens and destroy tumor cells. The radiolabeled minibody [89Zr]Zr-Df-IAB22M2C has a high affinity for human CD8+ T cells and was already successfully tested in a phase I study. Here, we aimed to gain first clinical PET/MRI experience with the non-invasive assessment of the CD8+ T cell distribution in cancer patients by in vivo [89Zr]Zr-Df-IAB22M2C.Material and Methods: We investigated 8 patients with metastasized cancers undergoing ICT. Radiolabeling of Df-IAB22M2C with Zr-89 was performed according to Good Manufacturing Practice. Multiparametric PET/MRI was acquired 24 h after injection of 74.2±17.9 MBq [89Zr]Zr-Df-IAB22M2C. We analyzed the [89Zr]Zr-Df-IAB22M2C uptake within the metastases and primary and secondary lymphatic organs. Results: [89Zr]Zr-Df-IAB22M2C injection was tolerated well without noticeable side effects. The CD8 PET/MRI data acquisitions 24 hours post administration of [89Zr]Zr-Df-IAB22M2C revealed a good image quality with a relatively low background signal due to only low unspecific tissue uptake and marginal blood pool retention. Only two metastatic lesions showed a markedly increased tracer uptake in our cohort of patients. Furthermore, we observed a high interpatient variability in the [89Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs. Four out of five ICT patients exhibited a rather high [89Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Two of these four patients as well as two other patients yielded a pronounced [89Zr]Zr-Df-IAB22M2C uptake within non metastatic lymph nodes. Interestingly, cancer progression in ICT patients was associated with a relatively low [89Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver in 4 out of the 6 patients.Conclusion: Our first clinical experiences revealed the feasibility of [89Zr]Zr-Df-IAB22M2C PET/MRI to assess potential immune-related changes in the metastases and the primary and secondary lymphatic organs. According to our results, we hypothesize that alteration in the [89Zr]Zr-Df-IAB22M2C uptake in primary and secondary lymphoid organs might be associated with the response to ICT.

Multiparametric magnetic resonance imaging (mpMRI) is an integral component of prostate cancer diagnostics. According to the S3 guidelines on prostate cancer, mpMRI should be used for the primary diagnostics of prostate cancer as well as in active surveillance (AS). Basically, mpMRI consists of high-resolution T2-weighted (T2w) sequences, diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences, which in turn are the basis for structured reporting according to the prostate imaging reporting and data system (PI-RADS) classification.Die multiparametrische Magnetresonanztomographie (mpMRT) ist fester Bestandteil der Prostatakarzinomdiagnostik. Sie soll gemäß der S3-Leitlinie „Prostatakarzinom“ zur Primärdiagnostik sowie in der aktiven Überwachung eingesetzt werden. Die mpMRT beinhaltet hochauflösende T2-gewichtete (T2w) Sequenzen, diffusionsgewichtete („diffusion-weighted imaging“, DWI) und dynamische kontrastmittelgestützte Sequenzen (DCE), welche Grundlage für die Befundung gemäß der PI-RADS(Prostate Imaging Reporting and Data System)-Klassifikation sind.

Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational study, we investigated whether noninvasive in vivo positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is capable of detecting immunotherapy-associated metabolic changes in the primary and secondary lymphoid organs and whether this detection enables the prediction of a successful anti-cancer immune response. Methods: RIP1-Tag2 mice with progressed endogenous insular cell carcinomas underwent a combined cancer immunotherapy consisting of CD4+ T cells plus monoclonal antibodies (mAbs) against programmed death ligand-1 (PD-L1) and lymphocyte activation gene-3 (LAG-3) or a sham treatment after radiation-mediated immune cell depletion. A second cohort of RIP1-Tag2 mice underwent exclusive checkpoint inhibitor therapy (CIT) using anti-PD-L1/LAG-3 mAbs or sham treatment without initial immune cell depletion to mimic the clinical situation. All mice were monitored by 18F-FDG-PET combined with anatomical magnetic resonance imaging (MRI). In addition, we retrospectively analyzed PET / computed tomography (CT) scans (PET/CT) regarding 18F-FDG uptake of CIT-treated metastatic melanoma patients in the spleen (n=23) and bone marrow (BM; n=20) as well as blood parameters (n=17-21). Results: RIP1-Tag2 mice with advanced insular cell carcinomas treated with combination immunotherapy exhibited significantly increased 18F-FDG uptake in the spleen compared to sham-treated mice. Histopathology of the spleens from treated mice revealed atrophy of the white pulp with fewer germinal centers and an expanded red pulp with hyperplasia of neutrophils than those of sham-treated mice. Immunohistochemistry and flow cytometry analyses of the spleens revealed a lower number of T cells and a higher number of neutrophils compared to those in the spleens of sham-treated mice. Flow cytometry of the BM showed enhanced activation of T cells following the treatment schemes that included checkpoint inhibitors. The ratio of 18F-FDG uptake at baseline to the uptake at follow-up in the spleens of exclusively CIT-treated RIP1-Tag2 mice was significantly enhanced, but the ratio was not enhanced in the spleens of the sham-treated littermates. Flow cytometry analysis confirmed a reduced number of T cells in the spleens of exclusively CIT-treated mice compared to that of sham-treated mice. A retrospective analysis of clinical 18F-FDG-PET/CT scans revealed enhanced 18F-FDG uptake in the spleens of some successfully CIT-treated patients with metastatic melanoma, but there were no significant differences between responders and non-responders. The analysis of the BM in clinical 18F-FDG-PET/CT scans with a computational segmentation tool revealed significantly higher baseline 18F-FDG uptake in patients who responded to CIT than in non-responders, and this relationship was independent of bone metastasis, even in the baseline scan. Conclusions: Thus, we are presenting the first translational study of solid tumors focusing on the metabolic patterns of primary and secondary lymphoid organs induced by the systemic immune response after CIT. We demonstrate that the widely available 18F-FDG-PET modality is an applicable translational tool that has high potential to stratify patients at an early time point.

Background: A transjugular intrahepatic portosystemic shunt (TIPS) is a common treatment for patients with portal hypertension. In these patients, the portal vein can be punctured under the guidance of cone-beam computed tomography (CBCT). Objectives: To compare standard-dose (SD) CBCT with low-dose (LD) CBCT, as three-dimensional (3D) intraprocedural guidance for transhepatic puncture in TIPS placement, in terms of image quality, radiation dose, technical success, and complications. Patients and Methods: A total of 44 patients were retrospectively enrolled in this study. Eighteen patients underwent LD-CBCT, while 26 patients underwent SD-CBCT for guiding the portal vein puncture. A quantitative assessment of image quality was performed by calculating the contrast-to-noise ratio (CNR) of the hepatic portal vein. This analysis was based on a five-point vascular visualization scale (VVS), ranging from optimal (score = 1) to non-diagnostic (score = 5), while a three-point Likert scale was used for motion artifacts (1 = no motion artifacts, 3 = blurred). Image streak artifacts were also rated from one to three, based on the image quality results. Technical success was also investigated, including the number of puncture attempts, time to successful portal vein access, and radiation dose of the TIPS procedure. Results: Based on the results, TIPS could be placed successfully in all cases. Neither VVS (LD-CBCT VVS: 2.78, SD-CBCT VVS: 2.54; P = 0.467), nor the procedure time showed any significant differences between the groups (LD-CBCT: 48.3 min, SD-CBCT: 40.2 min; P = 0.45). Moreover, the objective evaluation of image quality indicated the lower quality of LD-CBCT images; however, the difference was not statistically significant (LD-CBCT CNR: 1.1 ± 0.76, SD-CBCT CNR: 1.3 ± 1.1; P = 0.5). The median number of puncture attempts was the same for SD-CBCT and LD-CBCT (n = 3; range: 1 - 6). Also, the mean dose area product (DAP) was significantly lower in LD-CBCT as compared to SD-CBCT (LD-CBCT: 2733 ± 848 µGm2, SD-CBCT: 6119 ± 1677 µGm2; P < 0.0001). The total DAP was significantly lower using LD-CBCT (LD-CBCT: 14831 ± 9299 µGm2, SD-CBCT: 20985 ± 10127 µGm2; P = 0.047). Conclusion: Both SD-CBCT and LD-CBCT provided successful 3D guidance for portal vein puncture during TIPS creation. Although these methods did not differ significantly in terms of image quality, complications, or number of puncture attempts, LD-CBCT significantly reduced the radiation dose.

CD8+ cytotoxic T cells are key players in anti-cancer immune responses as they destroy MHC class I-dependent tumor cells. Therefore, the spatial distribution of CD8+ cytotoxic T cells might represent an important surrogate for the response to cancer immunotherapy including immune checkpoint inhibitor therapy ICT. The radiolabeled minibody [89Zr]Zr-Df-IAB22M2C is characterized by a high affinity to human CD8 and was already investigated in a phase I study. Here, we present our first experience with the non invasive in vivo assessment of the whole body CD8 T cell distribution in cancer patients using clinical [89Zr]Zr-Df-IAB22M2C PET/MRI. In total 8 patients with metastasized cancers (5 x malignant melanoma; 1 x choroidal melanoma, 1 x NSCLC and 1 x sarcoma) were studied before (n = 3) or during (n = 5) ICT. Multiparametric PET/MRI was performed 24 h after injection of 74.2±17.9 MBq [89Zr]Zr-Df-IAB22M2C (1.1 - 1.8 mg Df-IAB22M2C) on a Siemens Biograph mMR System (SiemensHealthineers, Erlangen, Germany). The whole body distribution of the [89Zr]Zr-Df-IAB22M2C tracer was analyzed with a special focus on tumors/metastases as well as primary and secondary lymphatic organs. The PET tracer [89Zr]Zr-Df-IAB22M2C was well tolerated without any reported side effects. The PET/MRI acquisitions 24h p.i. of [89Zr]Zr-Df-IAB22M2C revealed a comparably low background signal with only a minor blood pool and unspecific tissue retention. Regarding the primary and secondary lymphoid organs we observed a high interpatient variability of the tracer uptake. Four out of five patients with previous ICT exhibited a relatively high [89Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Also a large number of non metastatic lymph nodes yielded a pronounced [89Zr]Zr-Df-IAB22M2C uptake in four patients. Strikingly, a low [89Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver (liver/spleen ratio < 10) was observed in 4 out of the 5 patients with cancer progression during ICT. Interestingly, only one metastasis with an intense tracer was detected in this patient cohort. This first clinical experiences revealed the feasibility to assess potential immune-related changes by [89Zr]Zr-Df-IAB22M2C PET/MRI. Considering these results we hypothesize that the whole body distribution of CD8+ cytotoxic T-cells assessed by non-invasive in vivo [89Zr]Zr-Df-IAB22M2C PET/MRI might be associated with the response to cancer immunotherapy which needs to be investigated in subsequent prospective trials. Citation Format: Johannes Schwenck, Dominik Sonanini, Walter Ehrlichmann, Gabriele Kienzle, Gerald Reischl, Pascal Krezer, Ian Wilson, Ron Korn, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Ferdinand Seith, Andrea Forschner, Thomas Eigentler, Lars Zender, Martin Röcken, Bernd Pichler, Lukas Flatz, Manfred Kneilling, Christian la Fougere. Imaging of CD8+ cytotoxic T-cells by Zr-89-Df-IAB22M2C PET/MRI: First clinical experience in patients with metastatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB058.

OBJECTIVES The aim of this study was to investigate the impact of a novel edge enhancement and iterative denoising algorithm in 1.5-T T1-weighted dynamic contrast-enhanced (DCE) gradient echo (GRE) magnetic resonance imaging of the abdomen on image quality, noise levels, diagnostic confidence, and lesion detectability. MATERIALS AND METHODS Fifty patients who underwent a clinically indicated magnetic resonance imaging with DCE imaging of the abdomen between June and August 2020 were included in this retrospective, monocentric, institutional review board-approved study. For DCE imaging, a series of 3 volume interpolated breath-hold examinations (VIBEs) was performed. The raw data of all DCE imaging studies were processed twice, once using standard reconstruction (DCES) and again using an edge enhancement and iterative denoising approach (DCEDE). All imaging studies were randomly reviewed by 2 radiologists independently regarding noise levels, arterial contrast, sharpness of vessels, overall image quality, and diagnostic confidence using a Likert scale ranging from 1 to 4, with 4 being the best. Furthermore, lesion detectability was evaluated using the same ranking system. RESULTS All 50 imaging studies were successfully reconstructed with both methods. Interreader agreement (Cohen κ) was substantial to perfect for both readers. Arterial contrast and sharpness of vessels were rated superior by both readers with a median of 4 in DCEDE versus a median of 3 in DCES (P < 0.001). Furthermore, noise levels as well as overall image quality were rated higher with a median of 4 in DCEDE compared with a median of 3 in DCES (P < 0.001). Lesion detectability was evaluated to be superior in DCEDE with a median of 4 versus DCES with a median of 3 (P < 0.001). Consequently, diagnostic confidence was also rated to be superior in DCEDE with a median of 4 versus DCES with a median of 3 (P < 0.001). CONCLUSIONS Iterative denoising and edge enhancement are feasible in DCE imaging of the abdomen providing superior arterial contrast, noise levels, and overall image quality. Furthermore, lesion detectability and diagnostic confidence were significantly improved using this novel reconstruction method. Further reduction of acquisition time might be possible via reduction of increased noise levels using this presented method.

BACKGROUND Quantitative assessment of pulmonary blood flow and visualization of its temporal and spatial distribution without contrast media is of clinical significance. PURPOSE To assess the potential of electrocardiogram (ECG)-triggered pseudocontinuous arterial spin labeling (PCASL) imaging with balanced steady-state free-precession (bSSFP) readout to measure lung perfusion under free-breathing (FB) conditions and to study temporal and spatial characteristics of pulmonary blood flow. STUDY TYPE Prospective, observational. SUBJECTS Fourteen volunteers; three patients with pulmonary embolism. FIELD STRENGTH/SEQUENCES 1.5T, PCASL-bSSFP. ASSESSMENT The pulmonary trunk was labeled during systole. The following examinations were performed: 1) FB and timed breath-hold (TBH) examinations with a postlabeling delay (PLD) of 1000 msec, and 2) TBH examinations with multiple PLDs (100-1500 msec). Scan-rescan measurements were performed in four volunteers and one patient. Images were registered and the perfusion was evaluated in large vessels, small vessels, and parenchyma. Mean structural similarity indices (MSSIM) was computed and time-to-peak (TTP) of parenchymal perfusion in multiple PLDs was evaluated. Image quality reading was performed with three independent blinded readers. STATISTICAL TESTS Wilcoxon test to compare MSSIM, perfusion, and Likert scores. Spearman's correlation to correlate TTP and cardiac cycle duration. The repeatability coefficient (RC) and within-subject coefficient of variation (wCV) for scan-rescan measurements. Intraclass correlation coefficient (ICC) for interreader agreement. RESULTS Image registration resulted in a significant (P

Response assessment or prediction to checkpoint inhibitor therapy (CIT) is an unsolved problem in current routine diagnostics of patients with melanoma. Here, we evaluated very early changes of primary and secondary lymphoid organs under CIT in multiparametric [18F]-labeled fluorodeoxyglucose-positron emission tomography (18F-FDG-PET)/MRI as possible predictors of treatment response and investigated their correlation with baseline blood immune biomarkers. Between October 2014 and November 2017, 17 patients with unresectable melanoma (8 females; 65±11 years) undergoing CIT were prospectively evaluated using whole-body 18F-FDG-PET/MRI before CIT start (t0), 2 weeks (t1) and 3 months after CIT initiation (t2). At each time point, the volume, the 18F-FDG-uptake and the mean apparent diffusion coefficient (ADC) of the spleen as well as the 18F-FDG uptake of the bone marrow were assessed. Relative lymphocyte count (RLC), relative eosinophil count (REC) and neutrophil-lymphocyte ratio (NLR) were assessed at baseline. Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics (iRECIST) and decisions from an interdisciplinary tumor board were used for treatment response evaluation at t2. iRECIST was compared with PET response criteria in solid tumors for image-based response evaluation at different time points. Comparative analysis was conducted with Mann-Whitney U test with false discovery rate correction for multiple testing and correlation coefficients were computed. In lymphoid organs, significant differences (p18F-FDG-uptake in the spleen at t1 and the increase of the uptake t1-t0 (responders/non-responders: standardized uptake value lean body mass 1.19/0.93; +49%/−1%). The best correlation coefficients to baseline biomarkers were found for the 18F-FDG-uptake in the spleen at t1: NLR, r=−0.46; RLC, r=0.43; REC, r=0.58 (p18F-FDG-uptake of bone marrow (+31%/−9%) at t1 and the ADCmean at t2 (+46%/+15%) compared with t0, however, not reaching significance. Our findings indicate that an effective systemic immune response in patients undergoing CIT can be detected as a significantly increased spleen activity in 18F-FDG-PET as early as 2 weeks after treatment initiation.Trial registration numberNCT03132090, DRKS00013925.

To evaluate fast non-enhanced protocols for abdominal PET/MRI in comparison to contrast-enhanced PET/CT with somatostatin receptor (SSR)-specific radiotracers regarding effectiveness of lesion detection in NET patients. This was a retrospective analysis of 29 patients (12 male, 57 ± 13 years) who underwent PET/CT and subsequently PET/MRI at the same day. Two readers evaluated independently four PET/MRI setups: (I) PET + T2 Half Fourier Acquisition Single Shot Turbo Spin Echo (T2 HASTE), (II) PET + T2 HASTE + T2-weighted spin-echo sequence (T2 TSE), III) PET + T2 HASTE + Diffusion Weighted Imaging (DWI) and (IV) PET + T2 HASTE + T2 TSE + DWI. A consensus reading of PET/MRI and PET/CT including follow-up examinations served as the reference standard for lesion-based analysis. Lesion sizes were assessed. Setup IV provided comparable overall detection rates as PET/CT in both readers: PET/MRI 91.5%/92.9% versus 89.7% in PET/CT. In liver and bone lesions (mean diameter: 1.9 and 1.5 cm), PET/MRI was equal or superior to PET/CT: 98%/98% versus 85% in PET/CT; 100%/95% versus 100% in PET/CT, but inferior in pancreatic lesions, small bowel lesions and lymph node metastases (mean diameter: 1.3, 0.5 and 1.8 cm). A non-enhanced MR protocol comprising T2 HASTE, T2 TSE and DWI for SSR-PET/MRI seems to provide comparable effectiveness in lesions detection as multiphase contrast-enhanced PET/CT. It might, therefore, serve as valid alternative, e.g., for follow-up examinations in patients with unresectable NET and kidney failure.

The aim of this study was to compare the diagnostic performance of simultaneous multislice diffusion-weighted imaging (DWI-SMS) with that of standard DWI (DWI-STD) in whole-body 3-T PET/MRI examination protocols in oncological patients. In a phantom study, we evaluated the apparent diffusion coefficients (ADC) from the two techniques. In ten volunteers, we assessed ADC values in different organs. In 20 oncological patients, we evaluated subjective image quality (Likert scale, 5 indicating excellent) and artefacts in different body regions. We also rated the conspicuity and acquired the ADC values of PET-positive tumorous lesions. The scan time for the whole-body DWI-SMS examinations was 40% shorter than the scan time for the DWI-STD examinations (84 s vs. 140 s per table position). The phantom and volunteer studies showed lower ADC values from DWI-SMS in the liver and muscle (psoas muscle 1.4 vs. 1.3). In patients, DWI-SMS provided poorer subjective image quality in the thoracoabdominal region (3.0 vs. 3.8, p = 0.02) and overall more artefacts (138 vs. 105). No significant differences regarding conspicuity and ADC values of lesions were found. DWI-SMS seems to provide reliable conspicuity and ADC values of tumorous lesions similar to those provided by DWI-STD. Therefore, although providing poorer image quality in certain regions, DWI-SMS can clearly reduce PET/MRI scan times in oncological patients. • DWI-SMS can reduce PET/MRI scan times in oncological patients. • DWI-SMS provides reliable ADC values and good lesion conspicuity similar to those provided by DWI-STD. • DWI-SMS may provide poorer image quality in regions with low signal.

Purpose: To develop a motion correction for Positron-Emission-Tomography (PET) using simultaneously acquired magnetic-resonance (MR) images within 90 s. Methods: A 90 s MR acquisition allows the generation of a cardiac and respiratory motion model of the body trunk. Thereafter, further diagnostic MR sequences can be recorded during the PET examination without any limitation. To provide full PET scan time coverage, a sensor fusion approach maps external motion signals (respiratory belt, ECG-derived respiration signal) to a complete surrogate signal on which the retrospective data binning is performed. A joint Compressed Sensing reconstruction and motion estimation of the subsampled data provides motion-resolved MR images (respiratory + cardiac). A 1-POINT DIXON method is applied to these MR images to derive a motion-resolved attenuation map. The motion model and the attenuation map are fed to the Customizable and Advanced Software for Tomographic Reconstruction (CASToR) PET reconstruction system in which the motion correction is incorporated. All reconstruction steps are performed online on the scanner via Gadgetron to provide a clinically feasible setup for improved general applicability. The method was evaluated on 36 patients with suspected liver or lung metastasis in terms of lesion quantification (SUVmax, SNR, contrast), delineation (FWHM, slope steepness) and diagnostic confidence level (3-point Likert-scale). Results: A motion correction could be conducted for all patients, however, only in 30 patients moving lesions could be observed. For the examined 134 malignant lesions, an average improvement in lesion quantification of 22%, delineation of 64% and diagnostic confidence level of 23% was achieved. Conclusion: The proposed method provides a clinically feasible setup for respiratory and cardiac motion correction of PET data by simultaneous short-term MRI. The acquisition sequence and all reconstruction steps are publicly available to foster multi-center studies and various motion correction scenarios.

The aim of the study was to evaluate if 18F-FDG-PET has the potential to detect complete responders to PD1-therapy in patients with unresectable metastasized melanoma two weeks after therapy initiation. Between September 2014 and May 2016, ten patients (four females; 65 ± 12 y) received a whole-body 18F-FDG-PET/MRI examination at three time points: Before therapy start (t0, base-line), two weeks (t1, study examination) and three months after treatment initiation (t2, reference standard). Therapy response was assessed with PET response criteria in solid tumors (PERCIST). Time to progression and overall survival (OS) were obtained for all patients. Three patients with partial metabolic response in PET at t1 turned out to have complete response at t2. No tumor relapse was observed in those patients so far (observation period: 265, 511 and 728 days, respectively). At t2, progressive metabolic disease (PMD) was seen in six patients from whom four showed PMD and two showed stable metabolic disease (SMD) at t1. OS in patients with PMD at t2 varied between 148 and 814 days. SMD at both t1 and t2 was seen in one patient, tumor progress was observed after 308 days. Our study indicates that whole-body 18F-FDG-PET might be able to reliably identify complete responders to PD1-therapy as early as two weeks after therapy initiation in stage IV melanoma patients. This might help to shorten therapy regimes and avoid unnecessary side effects in the future.

Purpose: Cancer immunotherapy depends on a systemic immune response, but the basic underlying mechanisms are still largely unknown. Despite the very successful and widespread use of checkpoint inhibitors in the clinic, the majority of cancer patients do not benefit from this type of treatment. In this translational study, we investigated whether noninvasive in vivo positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) is capable of detecting immunotherapy-associated metabolic changes in the primary and secondary lymphoid organs and whether this detection enables the prediction of a successful anti-cancer immune response. Methods: RIP1-Tag2 mice with progressed endogenous insular cell carcinomas underwent a combined cancer immunotherapy consisting of CD4+ T cells plus monoclonal antibodies (mAbs) against programmed death ligand-1 (PD-L1) and lymphocyte activation gene-3 (LAG-3) or a sham treatment after radiation-mediated immune cell depletion. A second cohort of RIP1-Tag2 mice underwent exclusive checkpoint inhibitor therapy (CIT) using anti-PD-L1/LAG-3 mAbs or sham treatment without initial immune cell depletion to mimic the clinical situation. All mice were monitored by 18F-FDG-PET combined with anatomical magnetic resonance imaging (MRI). In addition, we retrospectively analyzed PET / computed tomography (CT) scans (PET/CT) regarding 18F-FDG uptake of CIT-treated metastatic melanoma patients in the spleen (n=23) and bone marrow (BM; n=20) as well as blood parameters (n=17-21). Results: RIP1-Tag2 mice with advanced insular cell carcinomas treated with combination immunotherapy exhibited significantly increased 18F-FDG uptake in the spleen compared to sham-treated mice. Histopathology of the spleens from treated mice revealed atrophy of the white pulp with fewer germinal centers and an expanded red pulp with hyperplasia of neutrophils than those of sham-treated mice. Immunohistochemistry and flow cytometry analyses of the spleens revealed a lower number of T cells and a higher number of neutrophils compared to those in the spleens of sham-treated mice. Flow cytometry of the BM showed enhanced activation of T cells following the treatment schemes that included checkpoint inhibitors. The ratio of 18F-FDG uptake at baseline to the uptake at follow-up in the spleens of exclusively CIT-treated RIP1-Tag2 mice was significantly enhanced, but the ratio was not enhanced in the spleens of the sham-treated littermates. Flow cytometry analysis confirmed a reduced number of T cells in the spleens of exclusively CIT-treated mice compared to that of sham-treated mice. A retrospective analysis of clinical 18F-FDG-PET/CT scans revealed enhanced 18F-FDG uptake in the spleens of some successfully CIT-treated patients with metastatic melanoma, but there were no significant differences between responders and non-responders. The analysis of the BM in clinical 18F-FDG-PET/CT scans with a computational segmentation tool revealed significantly higher baseline 18F-FDG uptake in patients who responded to CIT than in non-responders, and this relationship was independent of bone metastasis, even in the baseline scan. Conclusions: Thus, we are presenting the first translational study of solid tumors focusing on the metabolic patterns of primary and secondary lymphoid organs induced by the systemic immune response after CIT. We demonstrate that the widely available 18F-FDG-PET modality is an applicable translational tool that has high potential to stratify patients at an early time point.

Purpose To enable fast and flexible high-resolution four-dimensional (4D) MRI of periodic thoracic/abdominal motion for motion visualization or motion-corrected imaging. Methods We proposed a Cartesian three-dimensional k-space sampling scheme that acquires a random combination of k-space lines in the ky/kz plane. A partial Fourier–like constraint compacts the sampling space to one half of k-space. The central k-space line is periodically acquired to allow an extraction of a self-navigated respiration signal used to populate a k-space of multiple breathing positions. The randomness of the acquisition (induced by periodic breathing pattern) yields a subsampled k-space that is reconstructed using compressed sensing. Local image evaluations (coefficient of variation and slope steepness through organs) reveal information about motion resolvability. Image quality is inspected by a blinded reading. Sequence and reconstruction method are made publicly available. Results The method is able to capture and reconstruct 4D images with high image quality and motion resolution within a short scan time of less than 2 min. These findings are supported by restricted-isometry-property analysis, local image evaluation, and blinded reading. Conclusion The proposed method provides a clinical feasible setup to capture periodic respiratory motion with a fast acquisition protocol and can be extended by further surrogate signals to capture additional periodic motions. Retrospective parametrization allows for flexible tuning toward the targeted applications. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine