Impact of surgical variables on residual glandular tissue in risk-reducing mastectomies: Results of a retrospective monocentric study from a center of the German consortium for hereditary breast and ovarian cancer.

PURPOSE: Residual glandular tissue (RGT) after risk reducing mastectomy (RRME) is associated with a risk of developing breast cancer for women with a familial predisposition. We aim to examine various surgery-related variables to make risk more easily assessable and to aid in decision-making. MATERIALS AND METHODS: Pre- and postoperative breast MRI scans from 2006 to 2021 of patients with proven pathogenic mutation were included. The postoperative remaining skin flap was recorded using distance measurements at 8 equally distributed clockwise points and retromamillary. Each breast was volumetrized, as well as existing RGT. Patient-related covariates were further recorded and their influence on RGT was investigated uni- and multivariately. RESULTS: 81 patients (49 with BRCA1, 24 with BRCA2, 9 with other mutations), who were on average 39 years old, had 117 breasts analyzed. The mean follow-up was 71 months. In multivariate analysis, the independent variable skin flap thickness had a positive effect (p ≤ 0.01), while surgeon experience negatively affected RGT (p ≤ 0.05). The incision type was found to impact RGT as well, with nipple-sparing mastectomy (NSM) with inframammary fold incision leading to more RGT (p ≤ 0.01 - p ≤ 0.05), and skin-sparing mastectomy (SSM) with an inverted T incision leading to less (p ≤ 0.01). CONCLUSION: Different surgical variables have an impact on postoperative RGT, which is an important tool to quantify the risk of developing breast cancer after RRME. In order to effectively consider these variables in future preoperative/intraoperative management, they must be carefully taken into account.

Factors Influencing Residual Glandular Breast Tissue after Risk-Reducing Mastectomy in Genetically Predisposed Individuals Detected by MRI Mammography.

PURPOSE: This study seeks to evaluate MR imaging morphological factors and other covariates that influence the presence of residual glandular tissue after risk-reducing mastectomy in patients with a familial predisposition. METHODS: We analyzed women of a high-risk collective with pathogenic mutation (BRCA1 (n = 49), BRCA2 (n = 24), or further mutation (n = 9)). A total of 117 breasts were analyzed, 63 left and 54 right, from a cohort of 81 patients, who were on average 40 years old. The mean follow-up was 63 months (range 12-180 months, SD = 39.67). Retrospective analysis of MR imaging data from 2006-2022 of patients of a high-risk collective (all carriers of a pathogenic mutation) with contralateral (RRCM) or bilateral risk-reducing mastectomy (RRBM) was performed. In the image data the remaining skin flap thickness by distance measurements at eight equally distributed, clockwise points and the retromamillary area, as well as by volumetry of each breast, was elected. Residual glandular tissue was also volumetrized. In addition, patient-related covariates were recorded and their influence on postoperative residual glandular tissue and skin flap thickness was analyzed by uni- and multivariate regressions. RESULTS: A significant association with postoperative residual glandular tissue was shown in multivariate analysis for the independent variables breast density, skin flap mean, and surgical method (all p-values < 0.01). A negatively significant association could be seen for the variables preoperative breast volume (p-values < 0.01) and surgeon experience (most p-values < 0.05-<0.1). CONCLUSION: Postoperative residual glandular tissue is an important tool for quantifying the risk of developing breast cancer after risk-reducing mastectomy. Different effects on residual glandular tissue were shown for the independent variables breast density, skin flap, surgical method, preoperative breast volume, and surgeon experience, so these should be considered in future surgical procedures preoperatively as well as postoperatively. Breast MRI has proven to be a suitable method to analyze the skin flap as well as the RGT.

Effects of Anti-Tumor Necrosis Factor Therapy on Osteoblastic Activity at Sites of Inflammatory and Structural Lesions in Radiographic Axial Spondyloarthritis: A Prospective Proof-of-Concept Study Using Positron Emission Tomography/Magnetic Resonance Imaging of the Sacroiliac Joints and Spine.

OBJECTIVE: Proof-of-concept trial to determine the effects of tumor necrosis factor inhibitor (TNFi) therapy on osteoblastic activity at sites of inflammatory and structural lesions in patients with radiographic axial spondyloarthritis (SpA), using fluorine 18-labeled NaF (18 F-NaF) positron emission tomography/magnetic resonance imaging (PET/MRI). METHODS: Sixteen patients with clinically active radiographic axial SpA were prospectively enrolled to receive TNFi treatment and undergo 18 F-NaF PET/MRI of the sacroiliac (SI) joints and spine at baseline and at a follow-up visit 3-6 months after treatment initiation. Three readers (1 for PET/MRI and 2 for conventional MRI) evaluated all images, blinded to time point. Bone marrow edema, structural lesions (i.e., fat lesions, sclerosis, erosions, and ankylosis), and 18 F-NaF uptake at SI joint quadrants and vertebral corners (VCs) were recorded. RESULTS: Overall, 11 male and 5 female patients (mean age ± SD 38.6 ± 12.0 years) were followed up for a mean duration of 4.6 months (range 3-6). 18 F-NaF PET/MRI was conducted on SI joints for 16 patients and the spine for 10; 128 SI joint quadrants and 920 VCs were analyzed at each time point. At baseline, 18 F-NaF uptake was demonstrated in 96.0% of SI joint quadrants with bone marrow edema, 94.2% with sclerosis, and 88.3% with fat lesions. At follow-up, 65.3% of SI joint quadrants with bone marrow edema (P < 0.001), 33.8% with sclerosis (P = 0.23), and 24.5% with fat lesions (P = 0.01) had less 18 F-NaF uptake, compared with baseline. For VCs, 18 F-NaF uptake at baseline was found in 81.5% of edges with sclerosis, 41.9% with fat lesions, and 33.7% with bone marrow edema. At follow-up, 73.5% of VCs with bone marrow edema (P = 0.01), 53.3% with fat lesions (P = 0.03), and 55.6% with sclerosis (P = 0.16) showed less 18 F-NaF uptake, compared with baseline. CONCLUSION: Anti-TNF antibody treatment led to a significant decrease in osteoblastic activity within 3-6 months, especially, but not solely, at sites of inflammation. Larger data sets are needed for confirmation of the antiosteoblastic effects of TNFi for the prevention of radiographic progression in axial SpA.

Is there a diagnostic benefit of late-phase abdomino-pelvic PET/CT after urination as part of whole-body 68 Ga-PSMA-11 PET/CT for restaging patients with biochemical recurrence of prostate cancer after radical prostatectomy?

BACKGROUND: To assess the diagnostic value of an additional late-phase PET/CT scan after urination as part of 68 Ga-PSMA-11 PET/CT for the restaging of patients with biochemically recurrent prostate cancer (BCR). METHODS: This retrospective trial included patients with BCR following radical prostatectomy, who underwent standard whole-body early-phase PET/CT performed 105 ± 45 min and an additional late-phase PET/CT performed 159 ± 13 min after injection of 68 Ga-PSMA-11. Late-phase PET/CT covered a body volume from below the liver to the upper thighs and was conducted after patients had used the bathroom to empty their urinary bladder. Early- and late-phase images were evaluated regarding lesion count, type, localisation, and SUVmax. Reference standard was histopathology and/or follow-up imaging. RESULTS: Whole-body early-phase PET/CT detected 93 prostate cancer lesions in 33 patients. Late-phase PET/CT detected two additional lesions in two patients, both local recurrences. In total, there were 57 nodal, 28 bone, and 3 lung metastases, and 7 local recurrences. Between early- and late-phase PET/CT, lymph node metastases showed a significant increase of SUVmax from 14.5 ± 11.6 to 21.5 ± 17.6 (p = 0.00007), translating to a factor of + 1.6. Benign lymph nodes in the respective regions showed a significantly lower increase of SUVmax of 1.4 ± 0.5 to 1.7 ± 0.5 (p = 0.0014, factor of + 1.2). Local recurrences and bone metastases had a SUVmax on late-phase PET/CT that was + 1.7 and + 1.1 times higher than the SUVmax on early-phase PET/CT, respectively. CONCLUSION: In patients with BCR following radical prostatectomy, an additional abdomino-pelvic late-phase 68 Ga-PSMA-11 PET/CT scan performed after emptying the urinary bladder may help to detect local recurrences missed on standard whole-body 68 Ga-PSMA-11 PET/CT. Lymph node metastases show a higher SUVmax and a stronger increase of SUVmax than benign lymph nodes on late-phase PET/CT, hence, biphasic 68 Ga-PSMA-11 PET/CT might help to distinguish between malignant and benign nodes. Bone metastases, and especially local recurrences, also demonstrate a metabolic increase over time.

Impact of Different Metal Artifact Reduction Techniques on Attenuation Correction of Normal Organs in 18F-FDG-PET/CT.

PURPOSE: To evaluate the impact of different metal artifact reduction algorithms on Hounsfield units (HU) and the standardized uptake value (SUV) in normal organs in patients with different metal implants. METHODS: This study prospectively included 66 patients (mean age of 66.02 ± 13.1 years) with 87 different metal implants. CT image reconstructions were performed using weighted filtered back projection (WFBP) as the standard method, metal artifact reduction in image space (MARIS), and an iterative metal artifacts reduction (iMAR) algorithm for large implants. These datasets were used for PET attenuation correction. HU and SUV measurements were performed in nine predefined anatomical locations: liver, lower lung lobes, descending aorta, thoracic vertebral body, autochthonous back muscles, pectoral muscles, and internal jugular vein. Differences between HU and SUV measurements were compared using paired t-tests. The significance level was determined as p = 0.017 using Bonferroni correction. RESULTS: No significant differences were observed between reconstructed images using iMAR and WFBP concerning HU and SUV measurements in liver (HU: p = 0.055; SUVmax: p = 0.586), lung (HU: p = 0.276; SUVmax: p = 1.0 for the right side and HU: p = 0.630; SUVmax: p = 0.109 for the left side), descending aorta (HU: p = 0.333; SUVmax: p = 0.083), thoracic vertebral body (HU: p = 0.725; SUVmax: p = 0.392), autochthonous back muscles (HU: p = 0.281; SUVmax: p = 0.839), pectoral muscles (HU: p = 0.481; SUVmax: p = 0.277 for the right side and HU: p = 0.313; SUVmax: p = 0.859 for the left side), or the internal jugular vein (HU: p = 0.343; SUVmax: p = 0.194). CONCLUSION: Metal artifact reduction algorithms such as iMAR do not alter the data information of normal organs not affected by artifacts.

Free-breathing 3D Stack of Stars GRE (StarVIBE) sequence for detecting pulmonary nodules in 18F-FDG PET/MRI.

BACKGROUND: The free-breathing T1-weighted 3D Stack of Stars GRE (StarVIBE) MR sequence potentially reduces artifacts in chest MRI. The purpose of this study was to evaluate StarVIBE for the detection of pulmonary nodules in 18F-FDG PET/MRI. MATERIAL AND METHODS: In this retrospective analysis, conducted on a prospective clinical trial cohort, 88 consecutive women with newly diagnosed breast cancer underwent both contrast-enhanced whole-body 18F-FDG PET/MRI and computed tomography (CT). Patients' chests were examined on CT as well as on StarVIBE and conventional T1-weighted VIBE and T2-weighted HASTE MR sequences, with CT serving as the reference standard. Presence, size, and location of all detectable lung nodules were assessed. Wilcoxon test was applied to compare nodule features and Pearson's, and Spearman's correlation coefficients were calculated. RESULTS: Out of 65 lung nodules detected in 36 patients with CT (3.7 ± 1.4 mm), StarVIBE was able to detect 31 (47.7%), VIBE 26 (40%) and HASTE 11 (16.8%), respectively. Overall, CT showed a significantly higher detectability than all MRI sequences combined (65 vs. 36, difference 44.6%, p < 0.001). The VIBE showed a significantly better detection rate than the HASTE (23.1%, p = 0.001). Detection rates between StarVIBE and VIBE did not significantly differ (7.7%, p = 0.27), but the StarVIBE showed a significant advantage detecting centrally located pulmonary nodules (66.7% vs. 16.7%, p = 0.031). There was a strong correlation in nodule size between CT and MRI sequences (HASTE: ρ = 0.80, p = 0.003; VIBE: ρ = 0.77, p < 0.001; StarVIBE: ρ = 0.78, p < 0.001). Mean image quality was rated as good to excellent for CT and MRI sequences. CONCLUSION: The overall lung nodule detection rate of StarVIBE was slightly, but not significantly, higher than conventional T1w VIBE and significantly higher than T2w HASTE. Detectability of centrally located nodules is better with StarVIBE than with VIBE. Nevertheless, all MRI analyses demonstrated considerably lower detection rates for small lung nodules, when compared to CT.

Prospective comparison of CT and 18F-FDG PET/MRI in N and M staging of primary breast cancer patients: Initial results.

OBJECTIVES: To compare the diagnostic accuracy of contrast-enhanced thoraco-abdominal computed tomography and whole-body 18F-FDG PET/MRI in N and M staging in newly diagnosed, histopathological proven breast cancer. MATERIAL AND METHODS: A total of 80 consecutive women with newly diagnosed and histopathologically confirmed breast cancer were enrolled in this prospective study. Following inclusion criteria had to be fulfilled: (1) newly diagnosed, treatment-naive T2-tumor or higher T-stage or (2) newly diagnosed, treatment-naive triple-negative tumor of every size or (3) newly diagnosed, treatment-naive tumor with molecular high risk (T1c, Ki67 >14%, HER2neu over-expression, G3). All patients underwent a thoraco-abdominal ceCT and a whole-body 18F-FDG PET/MRI. All datasets were evaluated by two experienced radiologists in hybrid imaging regarding suspect lesion count, localization, categorization and diagnostic confidence. Images were interpreted in random order with a reading gap of at least 4 weeks to avoid recognition bias. Histopathological results as well as follow-up imaging served as reference standard. Differences in staging accuracy were assessed using Mc Nemars chi2 test. RESULTS: CT rated the N stage correctly in 64 of 80 (80%, 95% CI:70.0-87.3) patients with a sensitivity of 61.5% (CI:45.9-75.1), a specificity of 97.6% (CI:87.4-99.6), a PPV of 96% (CI:80.5-99.3), and a NPV of 72.7% (CI:59.8-82.7). Compared to this, 18F-FDG PET/MRI determined the N stage correctly in 71 of 80 (88.75%, CI:80.0-94.0) patients with a sensitivity of 82.1% (CI:67.3-91.0), a specificity of 95.1% (CI:83.9-98.7), a PPV of 94.1% (CI:80.9-98.4) and a NPV of 84.8% (CI:71.8-92.4). Differences in sensitivities were statistically significant (difference 20.6%, CI:-0.02-40.9; p = 0.008). Distant metastases were present in 7/80 patients (8.75%). 18 F-FDG PET/MRI detected all of the histopathological proven metastases without any false-positive findings, while 3 patients with bone metastases were missed in CT (sensitivity 57.1%, specificity 95.9%). Additionally, CT presented false-positive findings in 3 patients. CONCLUSION: 18F-FDG PET/MRI has a high diagnostic potential and outperforms CT in assessing the N and M stage in patients with primary breast cancer.

Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients.

OBJECTIVES: To compare the diagnostic performance of [18F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients. MATERIAL AND METHODS: A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [18F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ2 test was performed to compare sensitivity and specificity between the modalities. RESULTS: Forty-one bone metastases were present in 7/154 patients (4.5%). Both [18F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%). CONCLUSION: [18F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases. KEY POINTS: • [18F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients.

Comparison of pre- and post-contrast-enhanced attenuation correction using a CAIPI-accelerated T1-weighted Dixon 3D-VIBE sequence in 68Ga-DOTATOC PET/MRI.

OBJECTIVES: To investigate the influence of contrast agent administration on attenuation correction (AC) based on a CAIPIRINHA (CAIPI)-accelerated T1-weighted Dixon 3D-VIBE sequence in 68Ga-DOTATOC PET/MRI. MATERIAL AND METHODS: Fifty-one patients with neuroendocrine tumors underwent whole-body 68Ga-DOTATOC PET/MRI for tumor staging. Two PET reconstructions were performed using AC-maps that were created using a high-resolution CAIPI-accelerated Dixon-VIBE sequence with an additional bone atlas and truncation correction using the HUGE (B0 homogenization using gradient enhancement) method before and after application of Gadolinium (Gd)-based contrast agent. Standardized uptake values (SUVs) of 21 volumes of interest (VOIs) were compared between in both PET data sets per patient. A student's t-test for paired samples was performed to test for potential differences between both AC-maps and both reconstructed PET data sets. Bonferroni correction was performed to prevent α-error accumulation, p < 0.0024 was considered to indicate statistical significance. RESULTS: Significant quantitative differences between SUVmax were found in the perirenal fat (19.65 ±â€¯48.03 %, p < 0.0001), in the axillary fat (17.46 ±â€¯63.67 %, p < 0.0001) and in the dorsal subcutaneous fat on level of lumbar vertebral body L4 (10.26 ±â€¯25.29 %, p < 0.0001). Significant differences were also evident in the lungs apical (5.80 ±â€¯10.53 %, p < 0.0001), dorsal at the level of the pulmonary trunk (15.04 ±â€¯19.09 %, p < 0.0001) and dorsal in the basal lung (51.27 ±â€¯147.61 %, p < 0.0001). CONCLUSION: The administration of (Gd)-contrast agents in this study has shown a considerable influence on the AC-maps in PET/MRI and, consequently impacted quantification in the reconstructed PET data. Therefore, dedicated PET/MRI staging protocols have to be adjusted so that AC-map acquisition is performed prior to contrast agent administration.

Correlation between contrast enhancement, standardized uptake value (SUV), and diffusion restriction (ADC) with tumor grading in patients with therapy-naive neuroendocrine neoplasms using hybrid 68Ga-DOTATOC PET/MRI.

OBJECTIVES: To investigate a correlation between 68Ga-DOTATOC PET/MR imaging parameters such as arterial and venous contrast enhancement, diffusion restriction, and maximum standardized uptake value (SUVmax) with histopathological tumor grading in patients with neuroendocrine neoplasms (NEN). MATERIAL AND METHODS: A total of 26 patients with newly diagnosed, therapy-naive neuroendocrine neoplasms (NEN) were enrolled in this prospective study and underwent 68Ga-DOTATOC PET/MRI. Images were evaluated regarding NEN lesion number and location, predominant tumor signal intensity on precontrast T1w and T2w images and on postcontrast arterial and portal venous phase T1w images, apparent diffusion coefficient (ADC) and SUVmax. Histopathological tumor grading was assessed and related to PET/MRI features using Pearson's correlation coefficient and Fisher's exact t-test. A binary logistic regression analysis was performed to evaluate a potential relation with an aggressive tumor biology and odds ratios (OR) were calculated. RESULTS: There was a moderate negative correlation between arterial contrast enhancement and tumor grading (r=-0.35, p = 0.005), while portal venous enhancement showed a weak positive correlation with the Ki-67 index (r = 0.28, p = 0.008) and a non-significant positive correlation with tumor grading (r = 0.19, p = 0.063). Features that were significantly associated with an aggressive tumor biology were the presence of liver metastases (OR 2.6, p = 0.042), T1w hyperintensity in comparison to muscle (OR 12.7, p = 0.0001), arterial phase hyperenhancement (OR 1.4, p = 0.001), diffusion restriction (OR 2.8, p = 0.02) and SUVmax above the hepatic level (OR 7.0, p = 0.001). CONCLUSION: The study reveals that PET/MRI features might be useful for prediction of NEN grading and thus provide a preliminary assessment of tumor aggressiveness.

Prospective Correlation of Prognostic Immunohistochemical Markers With SUV and ADC Derived From Dedicated Hybrid Breast 18F-FDG PET/MRI in Women With Newly Diagnosed Breast Cancer.

PURPOSE: The aim of this study was to correlate prognostically relevant immunohistochemical parameters of breast cancer with simultaneously acquired SUVs and apparent diffusion coefficient (ADC) values derived from hybrid breast PET/MRI. PATIENTS AND METHODS: Fifty-six women with newly diagnosed, therapy-naive, histologically proven breast cancer (mean age, 54.1 ± 12.0 years) underwent dedicated prone 18F-FDG breast PET/MRI. Diffusion-weighted imaging (b-values: 0, 500, 1000 s/mm2) was performed simultaneously with the PET acquisition. A region of interest encompassing the entire primary tumor on each patient's PET/MRI scan was used to determine the glucose metabolism represented by maximum and mean SUV as well as into corresponding ADC maps to assess tumor cellularity represented by mean and minimum ADC values. Histopathological tumor grading and prognostically relevant immunohistochemical markers, that is, Ki67, progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2 (HER2), were assessed. Pearson correlation coefficients were calculated to compare SUV and ADC values as well as the immunohistochemically markers and molecular subtype. For the comparison with the tumor grading, a Wilcoxon test was used. RESULTS: A significant inverse correlation between SUV and ADC values derived from breast PET/MRI (r = -0.49 for SUVmean vs ADCmean; r = -0.43 for SUVmax vs ADCmin; both P's < 0.001) was found. Tumor grading and Ki67 both showed a positive correlation with SUVmean from breast PET/MRI (r = 0.37 and r = 0.32, P < 0.01). For immunohistochemical markers, HER2 showed an inverse correlation with ADC values from breast PET/MRI (r = -0.35, P < 0.01). Molecular subtypes significantly correlate with SUVmax and SUVmean (r = 0.52 and r = 0.42, both P's < 0.05). In addition, estrogen receptor expression showed an inverse correlation with SUVmax and SUVmean from breast PET/MRI (r = -0.45 and r = -0.42, P < 0.001). CONCLUSIONS: The present data show a correlation between increased glucose metabolism, cellularity, tumor grading, estrogen and HER2 expression, as well as molecular subtype of breast cancer primaries. Hence, simultaneous 18F-FDG PET and diffusion-weighted imaging from hybrid breast PET/MRI may serve as a predictive tool for identifying high-risk breast cancer patients in initial staging and guide-targeted therapy.

Correlation of the apparent diffusion coefficient (ADC) and standardized uptake values (SUV) with overall survival in patients with primary non-small cell lung cancer (NSCLC) using 18F-FDG PET/MRI.

OBJECTIVES: To investigate if the combined analysis of the apparent diffusion coefficient (ADC) and standardized uptake values (SUV) measured in 18F-fluoro-deoxy-glucose-positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) examinations correlates with overall survival in non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: A total of 92 patients with newly diagnosed, histopathologically proven NSCLC (44 women and 48 men, mean age 63.1 ±â€¯9.9y) underwent a dedicated thoracic 18F-FDG PET/MRI examination. A manually drawn polygonal region of interest (ROI), encompassing the entire primary tumor mass, was placed over the primary tumor on fused PET/MR images to determine the maximum and mean standardized uptake values (SUVmax; SUVmean) as well as on the ADC maps to quantify the mean and minimum ADC values (ADCmean, ADCmin). The impact of these parameters to predict patient's overall survival was tested using hazard ratios (HR). Pearson's correlation coefficients were calculated to assess dependencies between the different values. A p-value < 0.05 indicated statistical significance. RESULTS: In all 92 patients (n = 59 dead at time of retrospective data collection, mean time till death: 19 ±â€¯16 month, n = 33 alive, mean time to last follow-up: 56 ±â€¯22 month) the Hazard ratios (HR) as independent predictors for overall survival (OS) of SUVmax were 2.37 (95 % CI: 1.23-4.59, p = 0.008) and for SUVmean 1.85 (95 % CI: 1.05-3.26, p = 0.03) while ADCmin showed a HR of 0.95 (95 % CI: 0.57-1.59, p = 0.842) and ADCmean a HR of 2.01 (95 % CI: 1.2-3.38, p = 0.007). Furthermore, a combined analysis for SUVmax/ADCmean, SUVmax / ADCmin and SUVmean/ADCmean revealed a HR of 2.01 (95 % CI: 1.10-3.67, p = 0.02), 1.75 (95 % CI: 0.97-3.15, p = 0.058) and 1.78 (95 % CI: 1.02-3.10, p = 0.04). CONCLUSION: SUVmax and SUVmean of the primary tumor are predictors for OS in therapy-naive NSCLC patients, whereas the combined analysis of SUV and ADC values does not improve these results. Therefore, ADC values do not further enhance the diagnostic value of SUV as a prognostic biomarker in NSCLC.

Is there a connection between immunohistochemical markers and grading of lung cancer with apparent diffusion coefficient (ADC) and standardised uptake values (SUV) of hybrid 18F-FDG-PET/MRI?

INTRODUCTION: To correlate tumour grading and prognostic immunohistochemical markers of lung cancer with simultaneously acquired standardised uptake values (SUV) and apparent diffusion coefficient (ADC) derived from hybrid PET/MRI. METHODS: In this retrospective study, 55 consecutive patients (mean age 62.5 ± 9.2 years) with therapy-naïve, histologically proven lung cancer were included. All patients underwent whole-body PET/MRI using 18F-flourdeoxyglucose (18F-FDG) as a radiotracer. Diffusion-weighted imaging of the chest (DWI, b-values: 0, 500, 1000 s/mm2 ) was performed simultaneously with PET acquisition. Histopathological tumour grading was available in 43/55 patients. In 15/55 patients, immunohistochemical markers, that is, phospho-AKT Ser473 (pAKTS473), phosphorylated extracellular signal-regulated kinase (pERK), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (erbB2) were available. RESULTS: The average SUVmax, SUVmean, ADCmin and ADCmean in lung cancer primaries were 12.6 ± 5.9, 7.7 ± 4.6, 569.9 ± 96.1 s/mm2 and 825.8 ± 93.2 s/mm2 , respectively. We found a significant inverse correlation between the ADCmin and SUVmax (r = -0.58, P < 0.001) as well as between the ADCmin and SUVmean (r = -0.44, P < 0.001). Tumour grading showed a significant positive correlation with SUVmax and SUVmean (R = 0.34 and R = 0.31, both P < 0.05) and a significant inverse correlation with ADCmin and ADCmean (r = -0.30 and r = -0.40, both P < 0.05). In addition, erbB2 showed a significant inverse correlation with SUVmax and SUVmean (r = -0.50 and r = -0.49, both P < 0.05). The other immunohistochemical markers did not show any significant correlation. CONCLUSION: 18F-FDG-PET/MRI showed weak to moderate correlations between SUV, ADC, tumour grading and erbB2-expression of lung cancer. Hence, 18F-FDG-PET/MRI may, to some extent, offer complementary information to the histopathology of lung cancer, for the evaluation of tumour aggressiveness and treatment response.

Prospective evaluation of whole-body MRI and 18F-FDG PET/MRI in N and M staging of primary breast cancer patients.

OBJECTIVES: To evaluate and compare the diagnostic potential of whole-body MRI and whole-body 18F-FDG PET/MRI for N and M staging in newly diagnosed, histopathologically proven breast cancer. MATERIAL AND METHODS: A total of 104 patients (age 53.4 ± 12.5) with newly diagnosed, histopathologically proven breast cancer were enrolled in this study prospectively. All patients underwent a whole-body 18F-FDG PET/MRI. MRI and 18F-FDG PET/MRI datasets were evaluated separately regarding lesion count, lesion localization, and lesion characterization (malignant/benign) as well as the diagnostic confidence (5-point ordinal scale, 1-5). The N and M stages were assessed according to the eighth edition of the American Joint Committee on Cancer staging manual in MRI datasets alone and in 18F-FDG PET/MRI datasets, respectively. In the majority of lesions histopathology served as the reference standard. The remaining lesions were followed-up by imaging and clinical examination. Separately for nodal-positive and nodal-negative women, a McNemar chi2 test was performed to compare sensitivity and specificity of the N and M stages between 18F-FDG PET/MRI and MRI. Differences in diagnostic confidence scores were assessed by Wilcoxon signed rank test. RESULTS: MRI determined the N stage correctly in 78 of 104 (75%) patients with a sensitivity of 62.3% (95% CI: 0.48-0.75), a specificity of 88.2% (95% CI: 0.76-0.96), a PPV (positive predictive value) of 84.6% % (95% CI: 69.5-0.94), and a NPV (negative predictive value) of 69.2% (95% CI: 0.57-0.8). Corresponding results for 18F-FDG PET/MRI were 87/104 (83.7%), 75.5% (95% CI: 0.62-0.86), 92.2% (0.81-0.98), 90% (0.78-0.97), and 78.3% (0.66-0.88), showing a significantly better sensitivity of 18F-FDG PET/MRI determining malignant lymph nodes (p = 0.008). The M stage was identified correctly in MRI and 18F-FDG PET/MRI in 100 of 104 patients (96.2%). Both modalities correctly staged all 7 patients with distant metastases, leading to false-positive findings in 4 patients in each modality (3.8%). In a lesion-based analysis, 18F-FDG PET/MRI showed a significantly better performance in correctly determining malignant lesions (85.8% vs. 67.1%, difference 18.7% (95% CI: 0.13-0.26), p < 0.0001) and offered a superior diagnostic confidence compared with MRI alone (4.1 ± 0.7 vs. 3.4 ± 0.7, p < 0.0001). CONCLUSION: 18F-FDG PET/MRI has a better diagnostic accuracy for N staging in primary breast cancer patients and provides a significantly higher diagnostic confidence in lesion characterization than MRI alone. But both modalities bear the risk to overestimate the M stage.

Incidental 18F-FDG uptake in the colon: value of contrast-enhanced CT correlation with colonoscopic findings.

OBJECTIVES: To evaluate the impact of morphological information derived from contrast-enhanced CT in the characterization of incidental focal colonic uptake in 18F-FDG PET/CT examinations. METHODS: A total of 125 patients (female: n = 53, male: n = 72) that underwent colonoscopy secondary to contrast-enhanced, full-dose PET/CT without special bowel preparation were included in this retrospective study. PET/CT examinations were assessed for focal colonic tracer uptake in comparison with the background. Focal tracer uptake was correlated with morphological changes of the colonic wall in the contrast-enhanced CT images. Colonoscopy reports were evaluated for benign, inflammatory, polypoid, precancerous, and cancerous lesions verified by histopathology, serving as a reference standard. Sensitivity, specificity, PPV, NPV, and accuracy for detection of therapeutic relevant findings were calculated for (a) sole focal tracer uptake and (b) focal tracer uptake with correlating CT findings in contrast-enhanced CT. RESULTS: In 38.4% (48/125) of the patients, a focal 18F-FDG uptake was observed within 67 lesions. Malignant lesions were endoscopically and histopathologically diagnosed in eleven patients, and nine of these were detected by focal 18F-FDG uptake. A total of 34 lesions with impact on short- or long-term patient management (either being pre- or malignant) were detected. Sensitivity, Specificity, PPV, NPV, and accuracy for sole 18F-FDG uptake for this combined group were 54%, 69%, 29%, 85%, and 65%. Corresponding results for focal 18F-FDG uptake with correlating CT findings were 38%, 90%, 50%, 86%, and 80%. This resulted in a statistically significant difference for diagnostic accuracy (p = 0.0001) CONCLUSION: By analyzing additional morphological changes in contrast-enhanced CT imaging, the specificity of focal colonic 18F-FDG uptake for precancerous and cancerous lesions can be increased but leads to a considerate loss of sensitivity. Therefore, every focal colonic uptake should be followed up by colonoscopy.

Prospective comparison of whole-body MRI and 68Ga-PSMA PET/CT for the detection of biochemical recurrence of prostate cancer after radical prostatectomy.

PURPOSE: To assess whole-body magnetic resonance imaging (wb-MRI) for detection of biochemical recurrence in comparison to 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) in prostate cancer (Pca) patients after radical prostatectomy. METHODS: This was a prospective trial including 28 consecutive patients (mean age 65.3 ± 9.0 years) with newly documented biochemical recurrence of Pca (mean prostate-specific antigen, PSA, 2.09 ± 1.95 ng/ml) following radical prostatectomy. All patients underwent both wb-MRI including a dedicated pelvic imaging protocol and PET/CT with 166 ± 35 MBq 68Ga-PSMA within a time window of 11 ± 10 days. PET/CT and MRI datasets were separately evaluated regarding Pca lesion count, type, localization and diagnostic confidence (three-point Likert scale, 1-3) by two nuclear medicine specialists and two radiologists, respectively. The reference standard was based on histopathological results, PSA levels following targeted salvage irradiation and follow-up imaging. Lesion-based and patient-based detection rates were compared using the chi-squared test. Differences in diagnostic confidence were assessed using the Welch test. RESULTS: A total of 56 Pca lesions were detected in 20 of the 28 patients. 68Ga-PSMA PET/CT detected 56 of 56 lesions (100%) in 20 patients (71.4%), while wb-MRI detected 13 lesions (23.2%) in 11 patients (39.3%). The higher detection rate with 68Ga-PSMA PET/CT was statistically significant on both a per-lesion basis (p < 0.001) and a per-patient basis (p = 0.0167). In 8 patients (28.6%) no relapse was detectable by either modality. All lesions detected by wb-MRI were also detected by 68Ga-PSMA PET/CT. Additionally, 68Ga-PSMA PET/CT provided superior diagnostic confidence in identifying Pca lesions (2.7 ± 0.7 vs. 2.3 ± 0.6, p = 0.044). CONCLUSION: 68Ga-PSMA PET/CT significantly out-performed wb-MRI in the detection of biochemical recurrence in Pca patients after radical prostatectomy.

Potential of a machine-learning model for dose optimization in CT quality assurance.

OBJECTIVES: To evaluate machine learning (ML) to detect chest CT examinations with dose optimization potential for quality assurance in a retrospective, cross-sectional study. METHODS: Three thousand one hundred ninety-nine CT chest examinations were used for training and testing of the feed-forward, single hidden layer neural network (January 2016-December 2017, 60% male, 62 ± 15 years, 80/20 split). The model was optimized and trained to predict the volumetric computed tomography dose index (CTDIvol) based on scan patient metrics (scanner, study description, protocol, patient age, sex, and water-equivalent diameter (DW)). The root mean-squared error (RMSE) was calculated as performance measurement. One hundred separate, consecutive chest CTs were used for validation (January 2018, 60% male, 63 ± 16 years), independently reviewed by two blinded radiologists with regard to dose optimization, and used to define an optimal cutoff for the model. RESULTS: RMSE was 1.71, 1.45, and 1.52 for the training, test, and validation dataset, respectively. The scanner and DW were the most important features. The radiologists found dose optimization potential in 7/100 of the validation cases. A percentage deviation of 18.3% between predicted and actual CTDIvol was found to be the optimal cutoff: 8/100 cases were flagged as suboptimal by the model (range 18.3-53.2%). All of the cases found by the radiologists were identified. One examination was flagged only by the model. CONCLUSIONS: ML can comprehensively detect CT examinations with dose optimization potential. It may be a helpful tool to simplify CT quality assurance. CT scanner and DW were most important. Final human review remains necessary. A threshold of 18.3% between the predicted and actual CTDIvol seems adequate for CT quality assurance. KEY POINTS: • Machine learning can be integrated into CT quality assurance to improve retrospective analysis of CT dose data. • Machine learning may help to comprehensively detect dose optimization potential in chest CT, but an individual review of the results by an experienced radiologist or radiation physicist is required to exclude false-positive findings.

Prospective comparison of 18F-FDG PET/MRI and 18F-FDG PET/CT for thoracic staging of non-small cell lung cancer.

OBJECTIVES: To compare the diagnostic performance of 18F-FDG PET/MRI and 18F-FDG PET/CT for primary and locoregional lymph node staging in non-small cell lung cancer (NSCLC). METHODS: In this prospective study, a total of 84 patients (51 men, 33 women, mean age 62.5 ± 9.1 years) with histopathologically confirmed NSCLC underwent 18F-FDG PET/CT followed by 18F-FDG PET/MRI in a single injection protocol. Two readers independently assessed T and N staging in separate sessions according to the seventh edition of the American Joint Committee on Cancer staging manual for 18F-FDG PET/CT and 18F-FDG PET/MRI, respectively. Histopathology as a reference standard was available for N staging in all 84 patients and for T staging in 39 patients. Differences in staging accuracy were assessed by McNemars chi2 test. The maximum standardized uptake value (SUVmax) and longitudinal diameters of primary tumors were correlated using Pearson's coefficients. RESULTS: T stage was categorized concordantly in 18F-FDG PET/MRI and 18F-FDG PET/CT in 38 of 39 (97.4%) patients. Herein, 18F-FDG PET/CT and 18F-FDG PET/MRI correctly determined the T stage in 92.3 and 89.7% of patients, respectively. N stage was categorized concordantly in 83 of 84 patients (98.8%). 18F-FDG PET/CT correctly determined the N stage in 78 of 84 patients (92.9%), while 18F-FDG PET/MRI correctly determined the N stage in 77 of 84 patients (91.7%). Differences between 18F-FDG PET/CT and 18F-FDG PET/MRI in T and N staging accuracy were not statistically significant (p > 0.5, each). Tumor size and SUVmax measurements derived from both imaging modalities exhibited excellent correlation (r = 0.963 and r = 0.901, respectively). CONCLUSION: 18F-FDG PET/MRI and 18F-FDG PET/CT show an equivalently high diagnostic performance for T and N staging in patients suffering from NSCLC.