Mild Deficits in Fear Learning: Evidence from Humans and Mice with Cerebellar Cortical Degeneration.

Functional brain imaging studies in humans suggest involvement of the cerebellum in fear conditioning but do not allow conclusions about the functional significance. The main aim of the present study was to examine whether patients with cerebellar degeneration show impaired fear conditioning and whether this is accompanied by alterations in cerebellar cortical activations. To this end, a 2 d differential fear conditioning study was conducted in 20 cerebellar patients and 21 control subjects using a 7 tesla (7 T) MRI system. Fear acquisition and extinction training were performed on day 1, followed by recall on day 2. Cerebellar patients learned to differentiate between the CS+ and CS-. Acquisition and consolidation of learned fear, however, was slowed. Additionally, extinction learning appeared to be delayed. The fMRI signal was reduced in relation to the prediction of the aversive stimulus and altered in relation to its unexpected omission. Similarly, mice with cerebellar cortical degeneration (spinocerebellar ataxia type 6, SCA6) were able to learn the fear association, but retrieval of fear memory was reduced. In sum, cerebellar cortical degeneration led to mild abnormalities in the acquisition of learned fear responses in both humans and mice, particularly manifesting postacquisition training. Future research is warranted to investigate the basis of altered fMRI signals related to fear learning.

Central intra-lesional iron deposits as a possible novel imaging marker at 7 Tesla MRI in Susac Syndrome - an exploratory study.

BACKGROUND: Susac syndrome (SuS) is a rare autoimmune disease that leads to hearing impairment, visual field deficits, and encephalopathy due to an occlusion of precapillary arterioles in the brain, retina, and inner ear. Given the potentially disastrous outcome and difficulties in distinguishing SuS from its differential diagnoses, such as multiple sclerosis (MS), our exploratory study aimed at identifying potential new SuS-specific neuroimaging markers. METHODS: Seven patients with a definite diagnosis of SuS underwent magnetic resonance imaging (MRI) at 7 Tesla (7T), including T2* weighted and quantitative susceptibility mapping (QSM) sequences. T2 weighted hyperintense lesions were analyzed with regard to number, volume, localization, central vein sign, T1 hypointensity, and focal iron deposits in the center of SuS lesions ("iron dots"). Seven T MRI datasets from the same institute, comprising 75 patients with, among others, MS, served as controls. RESULTS: The "iron dot" sign was present in 71.4% (5/7) of the SuS patients, compared to 0% in our control cohort. Thus, sensitivity was 71.4% and specificity 100%. A central vein sign was only incidentally detected. CONCLUSION: We are the first to demonstrate this type of "iron dot" lesions on highly resolving 7T T2*w and QSM images in vivo as a promising neuroimaging marker of SuS, corroborating previous histopathological ex vivo findings.

Systematic evaluation of human soft tissue attenuation correction in whole-body PET/MR: Implications from PET/CT for optimization of MR-based AC in patients with normal lung tissue.

BACKGROUND: Attenuation correction (AC) is an important methodical step in positron emission tomography/magnetic resonance imaging (PET/MRI) to correct for attenuated and scattered PET photons. PURPOSE: The overall quality of magnetic resonance (MR)-based AC in whole-body PET/MRI was evaluated in direct comparison to computed tomography (CT)-based AC serving as reference. The quantitative impact of isolated tissue classes in the MR-AC was systematically investigated to identify potential optimization needs and strategies. METHODS: Data of n = 60 whole-body PET/CT patients with normal lung tissue and without metal implants/prostheses were used to generate six different AC-models based on the CT data for each patient, simulating variations of MR-AC. The original continuous CT-AC (CT-org) is referred to as reference. A pseudo MR-AC (CT-mrac), generated from CT data, with four tissue classes and a bone atlas represents the MR-AC. Relative difference in linear attenuation coefficients (LAC) and standardized uptake values were calculated. From the results two improvements regarding soft tissue AC and lung AC were proposed and evaluated. RESULTS: The overall performance of MR-AC is in good agreement compared to CT-AC. Lungs, heart, and bone tissue were identified as the regions with most deviation to the CT-AC (myocardium -15%, bone tissue -14%, and lungs ±20%). Using single-valued LACs for AC in the lung only provides limited accuracy. For improved soft tissue AC, splitting the combined soft tissue class into muscles and organs each with adapted LAC could reduce the deviations to the CT-AC to < ±1%. For improved lung AC, applying a gradient LAC in the lungs could remarkably reduce over- or undercorrections in PET signal compared to CT-AC (±5%). CONCLUSIONS: The AC is important to ensure best PET image quality and accurate PET quantification for diagnostics and radiotherapy planning. The optimized segment-based AC proposed in this study, which was evaluated on PET/CT data, inherently reduces quantification bias in normal lung tissue and soft tissue compared to the CT-AC reference.

The Potential of Iron Oxide Nanoparticle-Enhanced MRI at 7 T Compared With 3 T for Detecting Small Suspicious Lymph Nodes in Patients With Prostate Cancer.

BACKGROUND: Accurate detection of lymph node (LN) metastases in prostate cancer (PCa) is a challenging but crucial step for disease staging. Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) enables distinction between healthy LNs and nodes suspicious for harboring metastases. When combined with MRI at an ultra-high magnetic field, an unprecedented spatial resolution can be exploited to visualize these LNs. PURPOSE: The aim of this study was to explore USPIO-enhanced MRI at 7 T in comparison to 3 T for the detection of small suspicious LNs in the same cohort of patients with PCa. MATERIALS AND METHODS: Twenty PCa patients with high-risk primary or recurrent disease were referred to our hospital for an investigational USPIO-enhanced 3 T MRI examination with ferumoxtran-10. With consent, they underwent a 7 T MRI on the same day. Three-dimensional anatomical and T2*-weighted images of both examinations were evaluated blinded, with an interval, by 2 readers who annotated LNs suspicious for metastases. Number, size, and level of suspicion (LoS) of LNs were paired within patients and compared between field strengths. RESULTS: At 7 T, both readers annotated significantly more LNs compared with 3 T (474 and 284 vs 344 and 162), with 116 suspicious LNs on 7 T (range, 1-34 per patient) and 79 suspicious LNs on 3 T (range, 1-14 per patient) in 17 patients. For suspicious LNs, the median short axis diameter was 2.6 mm on 7 T (1.3-9.5 mm) and 2.8 mm for 3 T (1.7-10.4 mm, P = 0.05), with large overlap in short axis of annotated LNs between LoS groups. At 7 T, significantly more suspicious LNs had a short axis <2.5 mm compared with 3 T (44% vs 27%). Magnetic resonance imaging at 7 T provided better image quality and structure delineation and a higher LoS score for suspicious nodes. CONCLUSIONS: In the same cohort of patients with PCa, more and more small LNs were detected on 7 T USPIO-enhanced MRI compared with 3 T MRI. Suspicious LNs are generally very small, and increased nodal size was not a good indication of suspicion for the presence of metastases. The high spatial resolution of USPIO-enhanced MRI at 7 T improves structure delineation and the visibility of very small suspicious LNs, potentially expanding the in vivo detection limits of pelvic LN metastases in PCa patients.

Prediction of therapy response of breast cancer patients with machine learning based on clinical data and imaging data derived from breast [18F]FDG-PET/MRI.

PURPOSE: To evaluate if a machine learning prediction model based on clinical and easily assessable imaging features derived from baseline breast [18F]FDG-PET/MRI staging can predict pathologic complete response (pCR) in patients with newly diagnosed breast cancer prior to neoadjuvant system therapy (NAST). METHODS: Altogether 143 women with newly diagnosed breast cancer (54 ± 12 years) were retrospectively enrolled. All women underwent a breast [18F]FDG-PET/MRI, a histopathological workup of their breast cancer lesions and evaluation of clinical data. Fifty-six features derived from positron emission tomography (PET), magnetic resonance imaging (MRI), sociodemographic / anthropometric, histopathologic as well as clinical data were generated and used as input for an extreme Gradient Boosting model (XGBoost) to predict pCR. The model was evaluated in a five-fold nested-cross-validation incorporating independent hyper-parameter tuning within the inner loops to reduce the risk of overoptimistic estimations. Diagnostic model-performance was assessed by determining the area under the curve of the receiver operating characteristics curve (ROC-AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy. Furthermore, feature importances of the XGBoost model were evaluated to assess which features contributed most to distinguish between pCR and non-pCR. RESULTS: Nested-cross-validation yielded a mean ROC-AUC of 80.4 ± 6.0% for prediction of pCR. Mean sensitivity, specificity, PPV, and NPV of 54.5 ± 21.3%, 83.6 ± 4.2%, 63.6 ± 8.5%, and 77.6 ± 8.1% could be achieved. Histopathological data were the most important features for classification of the XGBoost model followed by PET, MRI, and sociodemographic/anthropometric features. CONCLUSION: The evaluated multi-source XGBoost model shows promising results for reliably predicting pathological complete response in breast cancer patients prior to NAST. However, yielded performance is yet insufficient to be implemented in the clinical decision-making process.

Recurrent prostate cancer: combined role for MRI and PSMA-PET in 68Ga-PSMA-11 PET/MRI.

OBJECTIVES: To investigate the specific strengths of MRI and PET components in 68Ga-PSMA-11 PET/MRI for staging of patients with biochemically recurrent prostate cancer (PCa). METHODS: Patients with biochemical recurrence of PCa and contrast-enhanced whole-body 68Ga-PSMA-11 PET/MRI including a dedicated pelvic multiparametric MRI were included in this retrospective study. Imaging datasets of MRI and PET were evaluated separately regarding local PCa recurrence (Tr), pelvic lymph node metastases (N1), distant lymph node metastases (M1a), bone metastases (M1b), and soft tissue metastases (M1c) according to PROMISE version 1. Data evaluation was performed patient- and region-/lesion-based. Cox regression revealed a PSA of 1.69 ng/mL as a cut-off for subgroup analysis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were evaluated for each image component. Differences in staging accuracy were assessed using the Wilcoxon and McNemar test. RESULTS: Altogether 102 patients (mean aged 68 ± 8 years, median PSA 1.33 ng/mL) were included. PCa was found in 70/102 (68%) patients. Accuracy of MRI in the detection of Tr, N1, M + , M1a, and M1b was 100%, 79%, 90%, 97%, and 95% for PSA < 1.69 ng/mL and 100%, 87%, 87%, 91%, and 96% for PSA > 1.69 ng/mL. Accuracy of 68Ga-PSMA-11 PET was 93%, 97%, 93%, 98%, and 100% for PSA < 1.69 ng/mL and 87%, 91%, 96%, 100%, and 96% for PSA > 1.69 ng/mL. CONCLUSIONS: Combined assessment of 68Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence. The MRI detected local recurrence of PCa more often whereas 68 Ga-PSMA-11 PET detected lymph node metastases more often, especially for PSA < 1.69 ng/mL. CLINICAL RELEVANCE STATEMENT: This study gives a scientific baseline to improve the understanding and reading of 68Ga-PSMA-11 PET/MRI imaging in patients with biochemically recurrent PCa by showing the specific strength of each imaging component. KEY POINTS: • Combining the individual modality strengths of 68Ga-PSMA-11 PET/MRI improves tumor localization in men with biochemical recurrence of prostate cancer. • MRI component of 68 Ga-PSMA-11 PET/MRI shows its strength in detecting local recurrence of prostate cancer, especially at PSA < 1.69 ng/mL. • 68 Ga-PSMA-11 PET component shows its strength in detecting local and distant lymph node metastases, especially at PSA < 1.69 ng/mL.

Safety and function of programmable ventriculo-peritoneal shunt valves: An in vitro 7 Tesla magnetic resonance imaging study.

OBJECTIVE: The quantity of ultra-high field MRI neuroimaging studies has rapidly increased. This study tests function, safety, and image artifacts of two frequently implanted programmable ventriculo-peritoneal (VP) shunt valves in a 7T MRI system. METHODS: All tests were performed using a whole-body 7T MRI system. Three proGAV 2.0 and 3 CODMAN CERTAS® Plus programmable VP-shunt valves were tested in three steps. 1) Deflection angle tests close to the bore opening at the location of a static magnetic field gradient of 3-5 T/m. 2) Valves were fixed on a spherical phantom in 3 positions (a. lateral, b. cranial, c. cranial with 22.5° tilt anteriorly) and assessed for keeping the programmed pressure setting and reprogrammability. 3) Valves were fixed on the phantom and positioned lateral in a radiofrequency head coil. MRI scans were performed for both models, including MPRAGE, GRE and SE sequences. RESULTS: Deflection angles were moderate (13°, 14°, 13°) for the proGAV valves and close to critical (43°, 43°, 41°) for the CODMAN valves at the test location. Taking a scaling factor of 2-3 for the maximum spatial magnetic field gradient accessible to a patient within the magnet bore into account renders both valves MR unsafe regarding ferromagnetic attraction. The proGAV valves kept the pressure settings in all positions and were reprogrammable in positions a. and b. In position c., reprogrammability was lost. The CODMAN valves changed their pressure setting and reprogrammability was lost in all positions. MR image signal homogeneity was unaltered in the phantom center, artifacts limit the assessability of structures in close vicinity to the valves. CONCLUSION: Both tested programmable VP-shunt valves are MR unsafe for 7T systems. Novel programming mechanisms using permanent magnets with sufficient magnetic coercivity or magnet-free mechanisms may allow the development of programmable VP-shunt valves that are conditional for 7T MR systems.

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology.

PREAMBLE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

[18F]FDG PET/MRI in children suffering from lymphoma: does MRI contrast media make a difference?

OBJECTIVES: Evaluate the influence of an MRI contrast agent application on primary and follow-up staging in pediatric patients with newly diagnosed lymphoma using [18F]FDG PET/MRI to avoid adverse effects and save time and costs during examination. METHODS: A total of 105 [18F]FDG PET/MRI datasets were included for data evaluation. Two different reading protocols were analyzed by two experienced readers in consensus, including for PET/MRI-1 reading protocol unenhanced T2w and/or T1w imaging, diffusion-weighted imaging (DWI), and [18F]FDG PET imaging and for PET/MRI-2 reading protocol an additional T1w post contrast imaging. Patient-based and region-based evaluation according to the revised International Pediatric Non-Hodgkin's Lymphoma (NHL) Staging System (IPNHLSS) was performed, and a modified standard of reference was applied comprising histopathology and previous and follow-up cross-sectional imaging. Differences in staging accuracy were assessed using the Wilcoxon and McNemar tests. RESULTS: In patient-based analysis, PET/MRI-1 and PET/MRI-2 both determined a correct IPNHLSS tumor stage in 90/105 (86%) exams. Region-based analysis correctly identified 119/127 (94%) lymphoma-affected regions. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for PET/MRI-1 and PET/MRI-2 were 94%, 97%, 90%, 99%, 97%, respectively. There were no significant differences between PET/MRI-1 and PET/MRI-2. CONCLUSIONS: The use of MRI contrast agents in [18F]FDG PET/MRI examinations has no beneficial effect in primary and follow-up staging of pediatric lymphoma patients. Therefore, switching to a contrast agent-free [18F]FDG PET/MRI protocol should be considered in all pediatric lymphoma patients. CLINICAL RELEVANCE STATEMENT: This study gives a scientific baseline switching to a contrast agent-free [18F]FDG PET/MRI staging in pediatric lymphoma patients. This could avoid side effects of contrast agents and saves time and costs by a faster staging protocol for pediatric patients. KEY POINTS: • No additional diagnostic benefit of MRI contrast agents at [18F]FDG PET/MRI examinations of pediatric lymphoma primary and follow-up staging • Highly accurate primary and follow-up staging of pediatric lymphoma patients at MRI contrast-free [18F]FDG PET/MRI.

Towards a fast PET/MRI protocol for breast cancer imaging: maintaining diagnostic confidence while reducing PET and MRI acquisition times.

OBJECTIVES: To investigate the diagnostic feasibility of a shortened breast PET/MRI protocol in breast cancer patients. METHODS: Altogether 90 women with newly diagnosed T1tumor-staged (T1ts) and T2tumor-staged (T2ts) breast cancer were included in this retrospective study. All underwent a dedicated comprehensive breast [18F]FDG-PET/MRI. List-mode PET data were retrospectively reconstructed with 20, 15, 10, and 5 min for each patient to simulate the effect of reduced PET acquisition times. The SUVmax/mean of all malign breast lesions was measured. Furthermore, breast PET data reconstructions were analyzed regarding image quality, lesion detectability, signal-to-noise ratio (SNR), and image noise (IN). The simultaneously acquired comprehensive MRI protocol was then shortened by retrospectively removing sequences from the protocol. Differences in malignant breast lesion detectability between the original and the fast breast MRI protocol were evaluated lesion-based. The 20-min PET reconstructions and the original MRI protocol served as reference. RESULTS: In all PET reconstructions, 127 congruent breast lesions could be detected. Group comparison and T1ts vs. T2ts subgroup comparison revealed no significant difference of subjective image quality between 20, 15, 10, and 5 min acquisition times. SNR of qualitative image evaluation revealed no significant difference between different PET acquisition times. A slight but significant increase of IN with decreasing PET acquisition times could be detected. Lesion SUVmax group comparison between all PET acquisition times revealed no significant differences. Lesion-based evaluation revealed no significant difference in breast lesion detectability between original and fast breast MRI protocols. CONCLUSIONS: Breast [18F]FDG-PET/MRI protocols can be shortened from 20 to below 10 min without losing essential diagnostic information. KEY POINTS: • A highly accurate breast cancer evaluation is possible by the shortened breast [18F]FDG-PET/MRI examination protocol. • Significant time saving at breast [18F]FDG-PET/MRI protocol could increase patient satisfaction and patient throughput for breast cancer patients at PET/MRI.

Germany's journey toward 14 Tesla human magnetic resonance.

Multiple sites within Germany operate human MRI systems with magnetic fields either at 7 Tesla or 9.4 Tesla. In 2013, these sites formed a network to facilitate and harmonize the research being conducted at the different sites and make this technology available to a larger community of researchers and clinicians not only within Germany, but also worldwide. The German Ultrahigh Field Imaging (GUFI) network has defined a strategic goal to establish a 14 Tesla whole-body human MRI system as a national research resource in Germany as the next progression in magnetic field strength. This paper summarizes the history of this initiative, the current status, the motivation for pursuing MR imaging and spectroscopy at such a high magnetic field strength, and the technical and funding challenges involved. It focuses on the scientific and science policy process from the perspective in Germany, and is not intended to be a comprehensive systematic review of the benefits and technical challenges of higher field strengths.

Numerical approach to investigate MR imaging artifacts from orthopedic implants at different field strengths according to ASTM F2119.

OBJECTIVE: This study presents an extended evaluation of a numerical approach to simulate artifacts of metallic implants in an MR environment. METHODS: The numerical approach is validated by comparing the artifact shape of the simulations and measurements of two metallic orthopedic implants at three different field strengths (1.5 T, 3 T, and 7 T). Furthermore, this study presents three additional use cases of the numerical simulation. The first one shows how numerical simulations can improve the artifact size evaluation according to ASTM F2119. The second use case quantifies the influence of different imaging parameters (TE and bandwidth) on the artifact size. Finally, the third use case shows the potential of performing human model artifact simulations. RESULTS: The numerical simulation approach shows a dice similarity coefficient of 0.74 between simulated and measured artifact sizes of metallic implants. The alternative artifact size calculation method presented in this study shows that the artifact size of the ASTM-based method is up to 50% smaller for complex shaped implants compared to the numerical-based approach. CONCLUSION: In conclusion, the numerical approach could be used in the future to extend MR safety testing according to a revision of the ASTM F2119 standard and for design optimization during the development process of implants.

Correlation between Imaging Markers Derived from PET/MRI and Invasive Acquired Biomarkers in Newly Diagnosed Breast Cancer.

PURPOSE: Evaluate the diagnostic potential of [18F]FDG-PET/MRI data compared with invasive acquired biomarkers in newly diagnosed early breast cancer (BC). METHODS: Altogether 169 women with newly diagnosed BC were included. All underwent a breast- and whole-body [18F]FDG-PET/MRI for initial staging. A tumor-adapted volume of interest was placed in the primaries and defined bone regions on each standard uptake value (SUV)/apparent diffusion coefficient (ADC) dataset. Immunohistochemical markers, molecular subtype, tumor grading, and disseminated tumor cells (DTCs) of each patient were assessed after ultrasound-guided biopsy of the primaries and bone marrow (BM) aspiration. Correlation analysis and group comparisons were assessed. RESULTS: A significant inverse correlation of estrogen-receptor (ER) expression and progesterone-receptor (PR) expression towards SUVmax was found (ER: r = 0.27, p < 0.01; PR: r = 0.19, p < 0.05). HER2-receptor expression showed no significant correlation towards SUV and ADC values. A significant positive correlation between Ki67 and SUVmax and SUVmean (r = 0.42 p < 0.01; r = 0.19 p < 0.05) was shown. Tumor grading significantly correlated with SUVmax and SUVmean (ρ = 0.36 and ρ = 0.39, both p's < 0.01). There were no group differences between SUV/ADC values of DTC-positive/-negative patients. CONCLUSIONS: [18F]FDG-PET/MRI may give a first impression of BC-receptor status and BC-tumor biology during initial staging by measuring glucose metabolism but cannot distinguish between DTC-positive/-negative patients and replace biopsy.

Grad-CAM Guided U-Net for MRI-based Pseudo-CT Synthesis.

In this paper, we address the task of image-to-image translation from MRI to CT domain. We propose a 2D U-Net-based deep learning approach for pseudo-CT synthesis that incorporates an additional Grad-CAM guided attention mechanism for superior image translation of bone regions. The suggested architecture consists of image-to-image translation and image classification modules. We first train our classifier to distinguish between MR and CT images. After that, we utilize it in combination with the Grad-CAM technique to provide additional guidance to our image-to-image translation network. We generate CT-class-specific localization maps for both CT and pseudo-CT images and then compare them. Thus, we force the image-to-image translation network to focus on relevant attributes of the CT class, such as bone structures, while learning to synthesize pseudo-CTs. The performance of the proposed approach is evaluated on the publicly available RIRE data set. Since MR and CT images in this data set are not correctly aligned with each other, we also briefly describe the applied image registration procedure. The experimental results are compared to the baseline U-Net model and demonstrate both qualitative and quantitative improvements, whereas significant performance gain is achieved for bone regions. Clinical Relevance- MRI-based pseudo-CT synthesis is essential for attenuation correction of PET in combined PET/MRI systems and plays a vital role in MRI-only radiotherapy planning. Accurate pseudo-CTs can prevent patients from harmful and unnecessary radiation exposure.

Lung Nodules Missed in Initial Staging of Breast Cancer Patients in PET/MRI-Clinically Relevant?

PURPOSE: The evaluation of the clinical relevance of missed lung nodules at initial staging of breast cancer patients in [18F]FDG-PET/MRI compared with CT. METHODS: A total of 152 patients underwent an initial whole-body [18F]FDG-PET/MRI and a thoracoabdominal CT for staging. Presence, size, shape and location for each lung nodule in [18F]FDG-PET/MRI was noted. The reference standard was established by taking initial CT and follow-up imaging into account (a two-step approach) to identify clinically-relevant lung nodules. Patient-based and lesion-based data analysis was performed. RESULTS: No patient with clinically-relevant lung nodules was missed on a patient-based analysis with MRI VIBE, while 1/84 females was missed with MRI HASTE (1%). Lesion-based analysis revealed 4/96 (4%, VIBE) and 8/138 (6%, HASTE) missed clinically-relevant lung nodules. The average size of missed lung nodules was 3.2 mm ± 1.2 mm (VIBE) and 3.6 mm ± 1.4 mm (HASTE) and the predominant location was in the left lower quadrant and close to the hilum. CONCLUSION: All patients with newly-diagnosed breast cancer and clinically-relevant lung nodules were detected at initial [18F]FDG-PET/MRI staging. However, due to the lower sensitivity in detecting lung nodules, a small proportion of clinically-relevant lung nodules were missed. Thus, supplemental low-dose chest CT after neoadjuvant therapy should be considered for backup.

Intra-Individual Comparison of 124I-PET/CT and 124I-PET/MR Hybrid Imaging of Patients with Resected Differentiated Thyroid Carcinoma: Aspects of Attenuation Correction.

BACKGROUND: This study evaluates the quantitative differences between 124-iodine (I) positron emission tomography/computed tomography (PET/CT) and PET/magnetic resonance imaging (PET/MR) in patients with resected differentiated thyroid carcinoma (DTC). METHODS: N = 43 124I PET/CT and PET/MR exams were included. CT-based attenuation correction (AC) in PET/CT and MR-based AC in PET/MR with bone atlas were compared concerning bone AC in the head-neck region. AC-map artifacts (e.g., dentures) were noted. Standardized uptake values (SUV) were measured in lesions in each PET data reconstruction. Relative differences in SUVmean were calculated between PET/CT and PET/MR with bone atlas. RESULTS: Overall, n = 111 124I-avid lesions were detected in all PET/CT, while n = 132 lesions were detected in PET/MR. The median in SUVmean for n = 98 congruent lesions measured in PET/CT was 12.3. In PET/MR, the median in SUVmean was 16.6 with bone in MR-based AC. CONCLUSIONS: 124I-PET/CT and 124I-PET/MR hybrid imaging of patients with DTC after thyroidectomy provides overall comparable quantitative results in a clinical setting despite different patient positioning and AC methods. The overall number of detected 124I-avid lesions was higher for PET/MR compared to PET/CT. The measured average SUVmean values for congruent lesions were higher for PET/MR.

Temporal dynamics of fMRI signal changes during conditioned interoceptive pain-related fear and safety acquisition and extinction.

Associative learning and memory mechanisms drive interoceptive signaling along the gut-brain axis, thus shaping affective-emotional reactions and behavior. Specifically, learning to predict potentially harmful, visceral pain is assumed to succeed within very few trials. However, the temporal dynamics of cerebellar and cerebral fMRI signal changes underlying early acquisition and extinction of learned fear signals and the concomitant evolvement of safety learning remain incompletely understood. 3 T fMRI data of healthy individuals from three studies were uniformly processed across the whole brain and the cerebellum. All studies employed differential delay conditioning (N = 94) with one visual cue (CS+) being repeatedly paired with visceral pain as unconditioned stimulus (US) while a second cue remained unpaired (CS-). During subsequent extinction (N = 51), all CS were presented without US. Behavioral results revealed increased CS+-aversiveness and CS--pleasantness after conditioning and diminished valence ratings for both CS following extinction. During early acquisition, the CS- induced linearly increasing neural activation in the insula, midcingulate cortex, hippocampus, precuneus as well as cerebral and cerebellar somatomotor regions. The comparison between acquisition and extinction phases yielded a CS--induced linear increase in the posterior cingulate cortex and precuneus during early acquisition, while there was no evidence for linear fMRI signal changes for the CS+ during acquisition and for both CS during extinction. Based on theoretical accounts of discrimination and temporal difference learning, these results suggest a gradual evolvement of learned safety cues that engage emotional arousal, memory, and cortical modulatory networks. As safety signals are presumably more difficult to learn and to discriminate from learned threat cues, the underlying temporal dynamics may reflect enhanced salience and prediction processing as well as increasing demands for attentional resources and the integration of multisensory information. Maladaptive responses to learned safety signals are a clinically relevant phenotype in multiple conditions, including chronic visceral pain, and can be exceptionally resistant to modification or extinction. Through sustained hypervigilance, safety seeking constitutes one key component in pain and stress-related avoidance behavior, calling for future studies targeting the mechanisms of safety learning and extinction to advance current cognitive-behavioral treatment approaches.

Multiparametric 18F-FDG PET/MRI-Based Radiomics for Prediction of Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The aim of this study was to assess whether multiparametric 18F-FDG PET/MRI-based radiomics analysis is able to predict pathological complete response in breast cancer patients and hence potentially enhance pretherapeutic patient stratification. METHODS: A total of 73 female patients (mean age 49 years; range 27-77 years) with newly diagnosed, therapy-naive breast cancer underwent simultaneous 18F-FDG PET/MRI and were included in this retrospective study. All PET/MRI datasets were imported to dedicated software (ITK-SNAP v. 3.6.0) for lesion annotation using a semi-automated method. Pretreatment biopsy specimens were used to determine tumor histology, tumor and nuclear grades, and immunohistochemical status. Histopathological results from surgical tumor specimens were used as the reference standard to distinguish between complete pathological response (pCR) and noncomplete pathological response. An elastic net was employed to select the most important radiomic features prior to model development. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated for each model. RESULTS: The best results in terms of AUCs and NPV for predicting complete pathological response in the entire cohort were obtained by the combination of all MR sequences and PET (0.8 and 79.5%, respectively), and no significant differences from the other models were observed. In further subgroup analyses, combining all MR and PET data, the best AUC (0.94) for predicting complete pathologic response was obtained in the HR+/HER2- group. No difference between results with/without the inclusion of PET characteristics was observed in the TN/HER2+ group, each leading to an AUC of 0.92 for all MR and all MR + PET datasets. CONCLUSION: 18F-FDG PET/MRI enables comprehensive high-quality radiomics analysis for the prediction of pCR in breast cancer patients, especially in those with HR+/HER2- receptor status.

The cerebellum contributes to context-effects during fear extinction learning: A 7T fMRI study.

The cerebellum is involved in the acquisition and consolidation of learned fear responses. Knowledge about its contribution to extinction learning, however, is sparse. Extinction processes likely involve erasure of memories, but there is ample evidence that at least part of the original memory remains. We asked the question whether memory persists within the cerebellum following extinction training. The renewal effect, that is the reoccurrence of the extinguished fear memory during recall in a context different from the extinction context, constitutes one of the phenomena indicating that memory of extinguished learned fear responses is not fully erased during extinction training. We performed a differential AB-A/B fear conditioning paradigm in a 7-Tesla (7T) MRI system in 31 young and healthy men. On day 1, fear acquisition training was performed in context A and extinction training in context B. On day 2, recall was tested in contexts A and B. As expected, participants learned to predict that the CS+ was followed by an aversive electric shock during fear acquisition training. Skin conductance responses (SCRs) were significantly higher to the CS+ compared to the CS- at the end of acquisition. Differences in SCRs vanished in extinction and reoccurred in the acquisition context during recall indicating renewal. Fitting SCR data, a deep neural network model was trained to predict the correct shock value for a given stimulus and context. Event-related fMRI analysis with model-derived prediction values as parametric modulations showed significant effects on activation of the posterolateral cerebellum (lobules VI and Crus I) during recall. Since the prediction values differ based on stimulus (CS+ and CS-) and context during recall, data provide support that the cerebellum is involved in context-related recall of learned fear associations. Likewise, mean ß values were highest in lobules VI and Crus I bilaterally related to the CS+ in the acquisition context during early recall. A similar pattern was seen in the vermis, but only on a trend level. Thus, part of the original memory likely remains within the cerebellum following extinction training. We found cerebellar activations related to the CS+ and CS- during fear acquisition training which likely reflect associative and non-associative aspects of the task. Cerebellar activations, however, were not significantly different for CS+ and CS-. Since the CS- was never followed by an electric shock, the cerebellum may contribute to associative learning related to the CS, for example as a safety cue.

Correlation Between Thrombus Signal Intensity and Aneurysm Wall Thickness in Partially Thrombosed Intracranial Aneurysms Using 7T Magnetization-Prepared Rapid Acquisition Gradient Echo Magnetic Resonance Imaging.

OBJECTIVE: The objective of this study is to investigate the relationship between the thrombus signal intensity and aneurysm wall thickness in partially thrombosed intracranial aneurysms in vivo with magnetization-prepared rapid acquisition gradient echo (MPRAGE) taken using 7T magnetic resonance imaging (MRI) and correlate the findings to wall instability. METHODS: Sixteen partially thrombosed intracranial aneurysms were evaluated using a 7T whole-body MR system with nonenhanced MPRAGE. To normalize the thrombus signal intensity, its highest signal intensity was compared to that of the anterior corpus callosum of the same subject, and the signal intensity ratio was calculated. The correlation between the thrombus signal intensity ratio and the thickness of the aneurysm wall was analyzed. Furthermore, aneurysmal histopathological specimens from six tissue samples were compared with radiological findings to detect any correlation. RESULTS: The mean thrombus signal intensity ratio was 0.57 (standard error of the mean [SEM] 0.06, range 0.25-1.01). The mean thickness of the aneurysm wall was 1.25 (SEM 0.08, range 0.84-1.55) mm. The thrombus signal intensity ratio significantly correlated with the aneurysm wall thickness (p < 0.01). The aneurysm walls with the high thrombus signal intensity ratio were significantly thicker. In histopathological examinations, three patients with a hypointense thrombus had fewer macrophages infiltrating the thrombus and a thin degenerated aneurysmal wall. In contrast, three patients with a hyperintense thrombus had abundant macrophages infiltrating the thrombus. CONCLUSION: The thrombus signal intensity ratio in partially thrombosed intracranial aneurysms correlated with aneurysm wall thickness and histologic features, indicating wall instability.