A novel approach to guide GD2-targeted therapy in pediatric tumors by PET and [64Cu]Cu-NOTA-ch14.18/CHO.

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

Additional Value of FDG-PET/MRI Complementary to Sentinel Lymphonodectomy for Minimal Invasive Lymph Node Staging in Patients with Endometrial Cancer: A Prospective Study.

BACKGROUND: Lymph node metastases (LNM) are rare in early-stage endometrial cancer, but a diagnostic systematic lymphadenectomy (LNE) is often performed to achieve reliable N-staging. Therefore, this prospective study aimed to evaluate the benefit of [18F]-Fluorodeoxyglucose (FDG) PET/MRI complementary to SPECT/CT guided sentinel lymphonodectomy (SLNE) for a less invasive N-staging Methods: 79 patients underwent a whole-body FDG-PET/MRI, SLN mapping with 99mTc-Nanocolloid SPECT/CT and indocyanine green (ICG) fluoroscopy followed by LNE which served as ground truth. RESULTS: FDG-PET/MRI was highly specific in N-staging (97.2%) but revealed limited sensitivity (66.7%) due to missed micrometastases. In contrast, bilateral SLN mapping failed more often in patients with macrometastases. The combination of SLN mapping and FDG-PET/MRI increased the sensitivity from 66.7% to 77.8%. Additional SLN labeling with dye (ICG) revealed a complete SLN mapping in 80% (8/10) of patients with failed or incomplete SLN detection in SPECT/CT, reducing the need for diagnostic systematic LNE up to 87%. FDG-PET/MRI detected para-aortic LNM in three out of four cases and a liver metastasis. CONCLUSIONS: The combination of FDG-PET/MRI and SLNE can reduce the need for diagnostic systematic LNE by up to 87%. PET/MRI complements the SLN technique particularly in the detection of para-aortic LNM and occasional distant metastases.

Selective Internal Radiotherapy (SIRT) and Chemosaturation Percutaneous Hepatic Perfusion (CS-PHP) for Metastasized Uveal Melanoma: A Retrospective Comparative Study.

Even with liver-targeted therapies, uveal melanoma with hepatic metastasis remains a challenge. The aim of this study was to compare the outcome of patients treated with either SIRT or CS-PHP. We included 62 patients with hepatic metastasized uveal melanoma (n = 34 with SIRT, receiving 41 cycles; n = 28 with CS-PHP, receiving 56 cycles) that received their treatments between 12/2013 and 02/2020 at a single center. We evaluated their response according to the RECIST 1.1, as well as progression-free survival (PFS) and overall survival (OS), after the initiation of the first cycle of the liver-directed treatment using Cox regression, adjusted via propensity score analysis for confounders, including the amount of hepatic involvement. The disease control rate was 18% for SIRT and 30% for CS-PHP. The median (range) of PFS was 127.5 (19-1912) days for SIRT and 408.5 (3-1809) days for CS-PHP; adjusted Cox regression showed no significant difference (p = 0.090). The median (range) of OS was 300.5 (19-1912) days for SIRT and 516 (5-1836) days for CS-PHP; adjusted Cox regression showed a significant difference (p = 0.006). In our patient cohort, patients treated with CS-PHP showed a significantly longer OS than patients treated with SIRT. CS-PHP might therefore be preferable for patients with liver-dominant metastatic uveal melanoma.

Impact of Tracer Dose Reduction in [18 F]-Labelled Fluorodeoxyglucose-Positron Emission Tomography ([18 F]-FDG)-PET) on Texture Features and Histogram Indices: A Study in Homogeneous Tissues of Phantom and Patient.

BACKGROUND: Histogram indices (HIs) and texture features (TFs) are considered to play an important role in future oncologic PET-imaging and it is unknown how these indices are affected by changes of tracer doses. A randomized undersampling of PET list mode data enables a simulation of tracer dose reduction. We performed a phantom study to compare HIs/TFs of simulated and measured tracer dose reductions and evaluated changes of HIs/TFs in the liver of patients with PETs from simulated reduced tracer doses. Overall, 42 HIs/TFs were evaluated in a NEMA phantom at measured and simulated doses (stepwise reduction of [18 F] from 100% to 25% of the measured dose). [18 F]-FDG-PET datasets of 15 patients were simulated from 3.0 down to 0.5 MBq/kgBW in intervals of 0.25 MBq/kgBW. HIs/TFs were calculated from two VOIs placed in physiological tissue of the right and left liver lobe and linear correlations and coefficients of variation analysis were performed. RESULTS: All 42 TFs did not differ significantly in measured and simulated doses (p > 0.05). Also, 40 TFs showed the same behaviour over dose reduction regarding differences in the same group (measured or simulated), and for 26 TFs a linear behaviour over dose reduction for measured and simulated doses could be validated. Out of these, 13 TFs could be identified, which showed a linear change in TF value in both the NEMA phantom and patient data and therefore should maintain the same informative value when transferred in a dose reduction setting. Out of this Homogeneity 2, Entropy and Zone size non-uniformity are of special interest because they have been described as preferentially considerable for tumour heterogeneity characterization. CONCLUSIONS: We could show that there was no significant difference of measured and simulated HIs/TFs in the phantom study and most TFs reveal a linear behaviour over dose reduction, when tested in homogeneous tissue. This indicates that texture analysis in PET might be robust to dose modulations.

Multiparametric Oncologic Hybrid Imaging: Machine Learning Challenges and Opportunities.

BACKGROUND: Machine learning (ML) is considered an important technology for future data analysis in health care. METHODS: 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. RESULTS AND CONCLUSION: 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. KEY POINTS: · ML provides a viable clinical solution for the reconstruction, processing, and analysis of hybrid imaging obtained from MRI, CT, and PET..

How [18F]-FDG-PET/CT Affects Clinical Management of Patients with Germ Cell Tumors in the Real World.

OBJECTIVE: The aim of this study was to evaluate the impact of PET/CT on clinical management of patients with germ cell tumors (GCTs) conducted in a real-world setting, including avoidance of invasive procedures, additional diagnostic imaging, and changes in treatment. METHODS: Patients with GCTs were prospectively enrolled into a PET/CT registry study between May 2013 and April 2021. Intended patient management prior and after PET/CT was documented using standardized questionnaires. Changes in oncologic staging and clinical management after PET/CT were recorded, including planned treatment and planned additional diagnostics. RESULTS: Forty-three male patients with GCTs were included consecutively in this study. After PET/CT, oncologic staging changed in 22/43 patients (51%), with upstaging in seven cases (16%), downstaging in ten cases (23%), and cancer relapse in five cases (11%). The number of patients with intended curative treatment remained stable, while a considerable change in intended therapeutic intervention was noted after PET/CT, with an increase in planned chemotherapy from three to eleven patients and a decrease in planned surgical resection from eleven to two patients. In addition, PET/CT contributed to preventing patients from intended invasive procedures including biopsy and surgery in 8/43 (19%) cases and from additional diagnostic procedures in 25 (58%) cases. CONCLUSION: With the use of FDG-PET/CT as a tool to guide patient management in GCTs, we observed a notable impact on clinical staging and a consequent reduction in the need for additional invasive and diagnostic procedures. These findings are expected to be even more consequential in the future as treatment modalities improve and the life expectancy of GCT patients further increases. KEY POINTS: PET/CT considerably influences the clinical stage of GCT patients. PET/CT has remarkable influence on the choice of therapeutic interventions and reduces additional diagnostic procedures.

Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans.

Objective: Patients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT. Methods: In total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK - EPI). Results: SUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: -0.519, p < 0.001) and GFRCDK - EPI (r: -0.555, p < 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p < 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points. Conclusion: This pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed "Accumulation Index" (ACI).

Whole-Body Magnetic Resonance Imaging (MRI) for Staging Melanoma Patients in Direct Comparison to Computed Tomography (CT): Results from a Prospective Positron Emission Tomography (PET)/CT and PET/MRI Study.

PURPOSE: The consideration of radiation exposure is becoming more important in metastatic melanoma due to improved prognoses. The aim of this prospective study was to investigate the diagnostic performance of whole-body (WB) magnetic resonance imaging (MRI) in comparison to computed tomography (CT) with 18F-FDG positron emission tomography (PET)/CT and 18F-PET/MRI together with a follow-up as the reference standard. METHODS: Between April 2014 and April 2018, a total of 57 patients (25 females, mean age of 64 ± 12 years) underwent WB-PET/CT and WB-PET/MRI on the same day. The CT and MRI scans were independently evaluated by two radiologists who were blinded to the patients' information. The reference standard was evaluated by two nuclear medicine specialists. The findings were categorized into different regions: lymph nodes/soft tissue (I), lungs (II), abdomen/pelvis (III), and bone (IV). A comparative analysis was conducted for all the documented findings. Inter-reader reliability was assessed using Bland-Altman procedures, and McNemar's test was utilized to determine the differences between the readers and the methods. RESULTS: Out of the 57 patients, 50 were diagnosed with metastases in two or more regions, with the majority being found in region I. The accuracies of CT and MRI did not show significant differences, except in region II where CT detected more metastases compared to MRI (0.90 vs. 0.68, p = 0.008). On the other hand, MRI had a higher detection rate in region IV compared to CT (0.89 vs. 0.61, p > 0.05). The level of agreement between the readers varied depending on the number of metastases and the specific region, with the highest agreement observed in region III and the lowest observed in region I. CONCLUSIONS: In patients with advanced melanoma, WB-MRI has the potential to serve as an alternative to CT with comparable diagnostic accuracy and confidence across most regions. The observed limited sensitivity for the detection of pulmonary lesions might be improved through dedicated lung imaging sequences.

Diagnostic Performance of Dynamic Whole-Body Patlak [18F]FDG-PET/CT in Patients with Indeterminate Lung Lesions and Lymph Nodes.

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.

Pulmonary magnetic resonance-guided online adaptive radiotherapy of locally advanced: the PUMA trial.

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 .

In vivo imaging of CD8+ T cells in metastatic cancer patients: first clinical experience with simultaneous [89Zr]Zr-Df-IAB22M2C PET/MRI.

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. CD8+ cytotoxic T cells are important gatekeepers for the therapeutic response to ICT and 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 successfully tested in a phase I study. Here, we aimed to gain the first clinical PET/MRI experience with the noninvasive assessment of the CD8+ T-cell distribution in cancer patients by in vivo [89Zr]Zr-Df-IAB22M2C with a distinct focus of identifying potential signatures of successful ICT. 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 [89Zr]Zr-Df-IAB22M2C uptake within the metastases and within 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 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 markedly increased tracer uptake in our cohort of patients. Furthermore, we observed high interpatient variability in [89Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs. Four out of five ICT patients exhibited rather high [89Zr]Zr-Df-IAB22M2C uptake in the bone marrow. Two of these four patients as well as two other patients yielded pronounced [89Zr]Zr-Df-IAB22M2C uptake within nonmetastatic 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. Lymph nodes with enhanced [89Zr]Zr-Df-IAB22M2C uptake revealed significantly reduced apparent diffusion coefficient (ADC) values in diffusion weighted MRI. Conclusion: Our first clinical experiences revealed the feasibility of [89Zr]Zr-Df-IAB22M2C PET/MRI in assessing potential immune-related changes in metastases and primary and secondary lymphatic organs. According to our results, we hypothesize that alterations in [89Zr]Zr-Df-IAB22M2C uptake in primary and secondary lymphoid organs might be associated with the response to ICT.

[Multiparametric MRI of the prostate: requirements and principles regarding diagnostic reporting]. / Die multiparametrische MRT der Prostata: Anforderungen und Grundlagen der Befundung.

Multiparametric MRI (mpMRI) is one of the primary diagnostic tools for detecting clinically relevant prostate cancer. It should be routinely used in addition to urological investigations owing to its higher diagnostic yield than systematic biopsies. However, combining targeted and systematic biopsies achieves the highest diagnostic rate. The Prostate Imaging Reporting and Data System (PI-RADS Version 2.1) standardizes the acquisition and interpretation of mpMRI of the prostate. It consists of high-resolution T2- and diffusion-weighted images, the corresponding apparent diffusion coefficient (ADC) maps, and a dynamic contrast-enhanced sequence. Reports describe the increasing likelihood of clinically significant prostate cancer with PI-RADS categories 1-5. The MRI sequence determining the PI-RADS category of a lesion depends on its location within the prostate: in the transitional zone, the T2-weighted sequence and, in the peripheral zone, the diffusion-weighted sequence are the primary determinants. The diffusion-weighted and contrast-enhanced sequences provide secondary classification for the transitional and peripheral zones, respectively. This review summarizes and illustrates the diagnostic criteria defined in PI-RADS 2.1. In addition, evidence for mpMRI of the prostate, its indication and implementation are described.

Free-breathing Arterial Spin Labeling MRI for the Detection of Pulmonary Embolism.

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 © RSNA, 2023.

Functional MRI to quantify perfusion changes of a renal allograft after embolization of an arteriovenous fistula.

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.

Multiparametric Dual-Time-Point [18F]FDG PET/MRI for Lymph Node Staging in Patients with Untreated FIGO I/II Cervical Carcinoma.

[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.

Development of a Hybrid-Imaging-Based Prognostic Index for Metastasized-Melanoma Patients in Whole-Body 18F-FDG PET/CT and PET/MRI Data.

Besides tremendous treatment success in advanced melanoma patients, the rapid development of oncologic treatment options comes with increasingly high costs and can cause severe life-threatening side effects. For this purpose, predictive baseline biomarkers are becoming increasingly important for risk stratification and personalized treatment planning. Thus, the aim of this pilot study was the development of a prognostic tool for the risk stratification of the treatment response and mortality based on PET/MRI and PET/CT, including a convolutional neural network (CNN) for metastasized-melanoma patients before systemic-treatment initiation. The evaluation was based on 37 patients (19 f, 62 ± 13 y/o) with unresectable metastasized melanomas who underwent whole-body 18F-FDG PET/MRI and PET/CT scans on the same day before the initiation of therapy with checkpoint inhibitors and/or BRAF/MEK inhibitors. The overall survival (OS), therapy response, metastatically involved organs, number of lesions, total lesion glycolysis, total metabolic tumor volume (TMTV), peak standardized uptake value (SULpeak), diameter (Dmlesion) and mean apparent diffusion coefficient (ADCmean) were assessed. For each marker, a Kaplan−Meier analysis and the statistical significance (Wilcoxon test, paired t-test and Bonferroni correction) were assessed. Patients were divided into high- and low-risk groups depending on the OS and treatment response. The CNN segmentation and prediction utilized multimodality imaging data for a complementary in-depth risk analysis per patient. The following parameters correlated with longer OS: a TMTV < 50 mL; no metastases in the brain, bone, liver, spleen or pleura; ≤4 affected organ regions; no metastases; a Dmlesion > 37 mm or SULpeak < 1.3; a range of the ADCmean < 600 mm2/s. However, none of the parameters correlated significantly with the stratification of the patients into the high- or low-risk groups. For the CNN, the sensitivity, specificity, PPV and accuracy were 92%, 96%, 92% and 95%, respectively. Imaging biomarkers such as the metastatic involvement of specific organs, a high tumor burden, the presence of at least one large lesion or a high range of intermetastatic diffusivity were negative predictors for the OS, but the identification of high-risk patients was not feasible with the handcrafted parameters. In contrast, the proposed CNN supplied risk stratification with high specificity and sensitivity.

Combination of PI-RADS score and mRNA urine test-A novel scoring system for improved detection of prostate cancer.

Available tests to detect clinically significant prostate cancer frequently lead to overdiagnosis and overtreatment. Our study assessed the feasibility of combining a urinary biomarker-based risk score (SelectMDx®) and multiparametric MRI outcomes in order to identify patients with prostate cancer on prostate biopsy with increased accuracy and reliability. Samples of 74 men with suspicion of prostate cancer and available multiparametric MRI were analysed in a prospective cross-sectional study design. First-voided urine for determination of HOXC6 and DLX1 mRNA levels was collected after digital rectal examination and prior to MRI/ultrasound fusion-guided prostate biopsy. All multiparametric MRI images were centrally reviewed by two experienced radiologists blinded for urine test results and biopsy outcome. The PI-RADS v2 was used. SelectMDx® score, PI-RADS and Gleason Sore were obtained. Associations between Gleason Score, PI-RADS scores and SelectMDx® were assessed using ANOVA and t-test. Sensitivity and specificity were assessed and evaluated as area-under-the-curve of the receiver operating characteristic. Upon biopsy, 59.5% of patients were diagnosed with prostate cancer, whereby 40.6% had high-grade prostate cancer (GS ≥ 7a). SelectMDx® scores were significantly higher for patients with positive biopsy findings (49.07 ± 25.99% vs. 22.00 ± 26.43%; p < 0.001). SelectMDx® scores increased with higher PI-RADS scores. Combining SelectMDx®, history of prior biopsy with benign histology and PI-RADS scores into a novel scoring system led to significant prostate cancer detection rates with tiered detection rate of 39%, 58%, 81% and 100% for Gleason grade group II, III, IV, and V, respectively. The area-under-the-curve for our novel sum score in receiver operating characteristic analysis was 0.84. The synergistic combination of two non-invasive tests into a sum score with increased sensitivity may help avoiding unnecessary biopsies for initial prostate cancer diagnosis. For confirmation, further prospective studies with larger sample sizes and univariate and multivariate regression analyses and decision curve analyses are required.