Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

Circulating tumour DNA (ctDNA) can be used to detect and profile residual tumour cells persisting after curative intent therapy1. The study of large patient cohorts incorporating longitudinal plasma sampling and extended follow-up is required to determine the role of ctDNA as a phylogenetic biomarker of relapse in early-stage non-small-cell lung cancer (NSCLC). Here we developed ctDNA methods tracking a median of 200 mutations identified in resected NSCLC tissue across 1,069 plasma samples collected from 197 patients enrolled in the TRACERx study2. A lack of preoperative ctDNA detection distinguished biologically indolent lung adenocarcinoma with good clinical outcome. Postoperative plasma analyses were interpreted within the context of standard-of-care radiological surveillance and administration of cytotoxic adjuvant therapy. Landmark analyses of plasma samples collected within 120 days after surgery revealed ctDNA detection in 25% of patients, including 49% of all patients who experienced clinical relapse; 3 to 6 monthly ctDNA surveillance identified impending disease relapse in an additional 20% of landmark-negative patients. We developed a bioinformatic tool (ECLIPSE) for non-invasive tracking of subclonal architecture at low ctDNA levels. ECLIPSE identified patients with polyclonal metastatic dissemination, which was associated with a poor clinical outcome. By measuring subclone cancer cell fractions in preoperative plasma, we found that subclones seeding future metastases were significantly more expanded compared with non-metastatic subclones. Our findings will support (neo)adjuvant trial advances and provide insights into the process of metastatic dissemination using low-ctDNA-level liquid biopsy.

Deep Learning to Estimate Cardiovascular Risk From Chest Radiographs : A Risk Prediction Study.

BACKGROUND: Guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD) recommend a risk calculator (ASCVD risk score) to estimate 10-year risk for major adverse cardiovascular events (MACE). Because the necessary inputs are often missing, complementary approaches for opportunistic risk assessment are desirable. OBJECTIVE: To develop and test a deep-learning model (CXR CVD-Risk) that estimates 10-year risk for MACE from a routine chest radiograph (CXR) and compare its performance with that of the traditional ASCVD risk score for implications for statin eligibility. DESIGN: Risk prediction study. SETTING: Outpatients potentially eligible for primary cardiovascular prevention. PARTICIPANTS: The CXR CVD-Risk model was developed using data from a cancer screening trial. It was externally validated in 8869 outpatients with unknown ASCVD risk because of missing inputs to calculate the ASCVD risk score and in 2132 outpatients with known risk whose ASCVD risk score could be calculated. MEASUREMENTS: 10-year MACE predicted by CXR CVD-Risk versus the ASCVD risk score. RESULTS: Among 8869 outpatients with unknown ASCVD risk, those with a risk of 7.5% or higher as predicted by CXR CVD-Risk had higher 10-year risk for MACE after adjustment for risk factors (adjusted hazard ratio [HR], 1.73 [95% CI, 1.47 to 2.03]). In the additional 2132 outpatients with known ASCVD risk, CXR CVD-Risk predicted MACE beyond the traditional ASCVD risk score (adjusted HR, 1.88 [CI, 1.24 to 2.85]). LIMITATION: Retrospective study design using electronic medical records. CONCLUSION: On the basis of a single CXR, CXR CVD-Risk predicts 10-year MACE beyond the clinical standard and may help identify individuals at high risk whose ASCVD risk score cannot be calculated because of missing data. PRIMARY FUNDING SOURCE: None.

Ultra-high-resolution photon-counting detector CT in evaluating coronary stent patency: a comparison to invasive coronary angiography.

OBJECTIVES: To determine the diagnostic accuracy of ultra-high-resolution photon-counting detector CT angiography (UHR PCD-CTA) for evaluating coronary stent patency compared to invasive coronary angiography (ICA). METHODS: Consecutive, clinically referred patients with prior coronary stent implantation were prospectively enrolled between August 2022 and March 2023 and underwent UHR PCD-CTA (collimation, 120 × 0.2 mm). Two radiologists independently analyzed image quality of the in-stent lumen using a 5-point Likert scale, ranging from 1 ("excellent") to 5 ("non-diagnostic"), and assessed all coronary stents for the presence of in-stent stenosis (≥ 50% lumen narrowing). The diagnostic accuracy of UHR PCD-CTA was determined, with ICA serving as the standard of reference. RESULTS: A total of 44 coronary stents in 18 participants (mean age, 83 years ± 6 [standard deviation]; 12 women) were included in the analysis. In 3/44 stents, both readers described image quality as non-diagnostic, whereas reader 2 noted a fourth stent to have non-diagnostic image quality. In comparison to ICA, UHR PCD-CTA demonstrated a sensitivity, specificity, and accuracy of 100% (95% CI [confidence interval] 47.8, 100), 92.3% (95% CI 79.1, 98.4), and 93.2% (95% CI 81.3, 98.6) for reader 1 and 100% (95% CI 47.8, 100), 87.2% (95% CI 72.6, 95.7), and 88.6% (95% CI 75.4, 96.2) for reader 2, respectively. Both readers observed a 100% negative predictive value (36/36 stents and 34/34 stents). Stent patency inter-reader agreement was 90.1%, corresponding to a substantial Cohen's kappa value of 0.72. CONCLUSIONS: UHR PCD-CTA enables non-invasive assessment of coronary stent patency with high image quality and diagnostic accuracy. CLINICAL RELEVANCE STATEMENT: Ultra-high-resolution photon-counting detector CT angiography represents a reliable and non-invasive method for assessing coronary stent patency. Its high negative predictive value makes it a promising alternative over invasive coronary angiography for the rule-out of in-stent stenosis. KEY POINTS: • CT-based evaluation of coronary stent patency is limited by stent-induced artifacts and spatial resolution. • Ultra-high-resolution photon-counting detector CT accurately evaluates coronary stent patency compared to invasive coronary angiography. • Photon-counting detector CT represents a promising method for the non-invasive rule-out of in-stent stenosis.

Value of virtual non-contrast images to identify uncomplicated cystic renal lesions: photon-counting detector CT vs. dual-energy integrating detector CT.

PURPOSE: To investigate the value of photon-counting detector CT (PCD-CT) derived virtual non-contrast (VNC) reconstructions to identify renal cysts in comparison with conventional dual-energy integrating detector (DE EID) CT-derived VNC reconstructions. MATERIAL AND METHODS: We prospectively enrolled consecutive patients with simple renal cysts (Bosniak classification-Version 2019, density ≤ 20 HU and/or enhancement ≤ 20 HU) who underwent multiphase (non-contrast, arterial, portal venous phase) PCD-CT and for whom non-contrast and portal venous phase DE EID-CT was available. Subsequently, VNC reconstructions were calculated for all contrast phases and density as well as contrast enhancement within the cysts were measured and compared. MRI and/or ultrasound served as reference standards for lesion classification. RESULTS: 19 patients (1 cyst per patient; age 69.5 ± 10.7 years; 17 [89.5%] male) were included. Density measurements on PCD-CT non-contrast and VNC reconstructions (arterial and portal venous phase) revealed no significant effect on HU values (p = 0.301). In contrast, a significant difference between non-contrast vs. VNC images was found for DE EID-CT (p = 0.02). For PCD-CT, enhancement for VNC reconstructions was < 20 HU for all evaluated cysts. DE EID-CT measurements revealed an enhancement of > 20 HU in five lesions (26.3%) using the VNC reconstructions, which was not seen with the non-contrast images. CONCLUSION: PCD-CT-derived VNC images allow for reliable and accurate characterization of simple cystic renal lesions similar to non-contrast scans whereas VNC images calculated from DE EID-CT resulted in substantial false characterization. Thus, PCD-CT-derived VNC images may substitute for non-contrast images and reduce radiation dose and follow-up imaging.

Photon-counting detector computed tomography for metal artifact reduction: a comparative study of different artifact reduction techniques in patients with orthopedic implants.

PURPOSE: Artifacts caused by metallic implants remain a challenge in computed tomography (CT). We investigated the impact of photon-counting detector computed tomography (PCD-CT) for artifact reduction in patients with orthopedic implants with respect to image quality and diagnostic confidence using different artifact reduction approaches. MATERIAL AND METHODS: In this prospective study, consecutive patients with orthopedic implants underwent PCD-CT imaging of the implant area. Four series were reconstructed for each patient (clinical standard reconstruction [PCD-CTStd], monoenergetic images at 140 keV [PCD-CT140keV], iterative metal artifact reduction (iMAR) corrected [PCD-CTiMAR], combination of iMAR and 140 keV monoenergetic [PCD-CT140keV+iMAR]). Subsequently, three radiologists evaluated the reconstructions in a random and blinded manner for image quality, artifact severity, anatomy delineation (adjacent and distant), and diagnostic confidence using a 5-point Likert scale (5 = excellent). In addition, the coefficient of variation [CV] and the relative quantitative artifact reduction potential were obtained as objective measures. RESULTS: We enrolled 39 patients with a mean age of 67.3 ± 13.2 years (51%; n = 20 male) and a mean BMI of 26.1 ± 4 kg/m2. All image quality measures and diagnostic confidence were significantly higher for the iMAR vs. non-iMAR reconstructions (all p < 0.001). No significant effect of the different artifact reduction approaches on CV was observed (p = 0.26). The quantitative analysis indicated the most effective artifact reduction for the iMAR reconstructions, which was higher than PCD-CT140keV (p < 0.001). CONCLUSION: PCD-CT allows for effective metal artifact reduction in patients with orthopedic implants, resulting in superior image quality and diagnostic confidence with the potential to improve patient management and clinical decision making.

Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial.

BACKGROUND: We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis. METHODS: In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0-1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m2) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab. The primary endpoint was 3-year invasive disease-free survival. Here, we report 10-year survival outcomes, assessed in all participants who received protocol-defined treatment, with exploratory analyses using the HER2DX genomic tool. This study is registered on ClinicalTrials.gov, NCT00542451, and is closed to accrual. FINDINGS: Between Oct 29, 2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%) was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and 272 (67·0%) had hormone receptor-positive disease. After a median follow-up of 10·8 years (IQR 7·1-11·4), among 406 patients included in the analysis population, we observed 31 invasive disease-free survival events, of which six (19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new contralateral breast cancers, six (19·4%) were distant recurrences, and ten (32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3% (95% CI 88·3-94·4), 10-year recurrence-free interval was 96·3% (95% CI 94·3-98·3), 10-year overall survival was 94·3% (95% CI 91·8-96·8), and 10-year breast cancer-specific survival was 98·8% (95% CI 97·6-100). HER2DX risk score as a continuous variable was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00-1·52]; p=0·047) and recurrence-free interval (1·45 [1·09-1·93]; p=0·011). INTERPRETATION: Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population. FUNDING: Genentech.

Accuracy of Ultrahigh-Resolution Photon-counting CT for Detecting Coronary Artery Disease in a High-Risk Population.

Background Recently introduced photon-counting CT may improve noninvasive assessment of patients with high risk for coronary artery disease (CAD). Purpose To determine the diagnostic accuracy of ultrahigh-resolution (UHR) coronary CT angiography (CCTA) in the detection of CAD compared with the reference standard of invasive coronary angiography (ICA). Materials and Methods In this prospective study, participants with severe aortic valve stenosis and clinically indicated CT for transcatheter aortic valve replacement planning were consecutively enrolled from August 2022 to February 2023. All participants were examined with a dual-source photon-counting CT scanner using a retrospective electrocardiography-gated contrast-enhanced UHR scanning protocol (tube voltage, 120 or 140 kV; collimation, 120 × 0.2 mm; 100 mL of iopromid; no spectral information). Subjects underwent ICA as part of their clinical routine. A consensus assessment of image quality (five-point Likert scale: 1 = excellent [absence of artifacts], 5 = nondiagnostic [severe artifacts]) and a blinded independent reading for the presence of CAD (stenosis ≥50%) were performed. UHR CCTA was compared with ICA using area under the receiver operating characteristic curve (AUC). Results Among 68 participants (mean age, 81 years ± 7 [SD]; 32 male, 36 female), the prevalence of CAD and prior stent placement was 35% and 22%, respectively. The overall image quality was excellent (median score, 1.5 [IQR, 1.3-2.0]). The AUC of UHR CCTA in the detection of CAD was 0.93 per participant (95% CI: 0.86, 0.99), 0.94 per vessel (95% CI: 0.91, 0.98), and 0.92 per segment (95% CI: 0.87, 0.97). Sensitivity, specificity, and accuracy, respectively, were 96%, 84%, and 88% per participant (n = 68); 89%, 91%, and 91% per vessel (n = 204); and 77%, 95%, and 95% per segment (n = 965). Conclusion UHR photon-counting CCTA provided high diagnostic accuracy in the detection of CAD in a high-risk population, including subjects with severe coronary calcification or prior stent placement. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Williams and Newby in this issue.

Myeloma bone disease imaging on a 1st-generation clinical photon-counting detector CT vs. 2nd-generation dual-source dual-energy CT.

OBJECTIVE: Subjective and objective image quality comparison of bone microstructure and disease-related abnormalities in multiple myeloma patients using a 1st-generation dual-source photon-counting detector CT(DS-PCD-CT) and a 2nd-generation dual-source dual-energy (energy-integrating detector) CT (DS-EID-CT). METHODS: Fifty multiple myeloma patients (mean age 67.7 ± 10.9 years,16 females) were prospectively enrolled. Unenhanced whole-body CTs were clinically indicated and performed on DS-EID-CT and DS-PCD-CT (median time difference: 12 months). DS-PCD-CT was performed in Quantumplus UHR mode and DS-EID-CT was performed using dual-energy mode. DS-PCD-CT kernel was set at Br64 with Quantum iterative reconstruction strength Q1; for DS-EID-CT a comparable I70f kernel with SAFIRE iterative reconstruction strength 1 was used. Two independent radiologists assessed image quality subjectively using a 5-point Likert scale considering delineation and sharpness of trabecular bone and lytic bone lesions in the spine and pelvic bones. Additionally, ImageJ was used for quantification of bony septa inside the cancellous bone and through or the edges of osteolysis. RESULTS: Overall quality as well as detectability and sharpness in the delineation of lytic bone lesions were superior for DS-PCD-CT compared with DS-EID-CT (p < 0.0001). The inter-reader agreement for subjective image quality readings showed excellent consistency(α = 94.2-98.8). CTDI and DLP mean values for DS-PCD-CT and DS-EID-CT were 1107.4 ± 247.6 mGy*cm and 8.2 ± 1.8 mGy vs. 1344.3 ± 204.6 mGy*cm and 10.1 ± 1.9 mGy. The quantitative metric for bone microstructure in the femoral head showed significantly better visualization of trabeculae in DS-PCD-CT compared with DS-EID-CT (p < 0.0001). Quantitative analyses of edge sharpness of osteolysis showed significant steeper edges for DS-PCD-CT (p < 0.0001). CONCLUSION: DS-PCD-CT significantly improves spatial resolution of bony microstructure and lytic bone lesions compared to DS-EID-CT. KEY POINTS: • Application of photon-counting detector CT is superior to dual-source dual-energy integrating detector in clinical workup of multiple myeloma patients. • Compared to energy integrating detectors, photon-counting detectors significantly increase the spatial resolution of bone microstructure including disease-related lytic bone lesions in patients with multiple myeloma.

Impact of different metal artifact reduction techniques in photon-counting computed tomography head and neck scans in patients with dental hardware.

OBJECTIVES: Metal artifacts remain a challenge in computed tomography. We investigated the potential of photon-counting computed tomography (PCD-CT) for metal artifact reduction using an iterative metal artifact reduction (iMAR) algorithm alone and in combination with high keV monoenergetic images (140 keV) in patients with dental hardware. MATERIAL AND METHODS: Consecutive patients with dental implants were prospectively included in this study and received PCD-CT imaging of the craniofacial area. Four series were reconstructed (standard [PCD-CTstd], monoenergetic at 140 keV [PCD-CT140keV], iMAR corrected [PCD-CTiMAR], combination of iMAR and 140 keV monoenergetic [PCD-CTiMAR+140keV]). All reconstructions were assessed qualitatively by four radiologists (independent and blinded reading on a 5-point Likert scale [5 = excellent; no artifact]) regarding overall image quality, artifact severity, and delineation of adjacent and distant anatomy. To assess signal homogeneity and evaluate the magnitude of artifact reduction, we performed quantitative measures of coefficient of variation (CV) and a region of interest (ROI)-based relative change in artifact reduction [PCD-CT/PCD-CTstd]. RESULTS: We enrolled 48 patients (mean age 66.5 ± 11.2 years, 50% (n = 24) males; mean BMI 25.2 ± 4.7 kg/m2; mean CTDIvol 6.2 ± 6 mGy). We found improved overall image quality, reduced artifacts and superior delineation of both adjacent and distant anatomy for the iMAR vs. non-iMAR reconstructions (all p < 0.001). No significant effect of the different artifact reduction approaches on CV was observed (p = 0.42). The ROI-based analysis indicated the most effective artifact reduction for the iMAR reconstructions, which was significantly higher compared to PCD-CT140keV (p < 0.001). CONCLUSION: PCD-CT offers highly effective approaches for metal artifact reduction with the potential to overcome current diagnostic challenges in patients with dental implants. CLINICAL RELEVANCE STATEMENT: Metallic artifacts pose a significant challenge in CT imaging, potentially leading to missed findings. Our study shows that PCD-CT with iMAR post-processing reduces artifacts, improves image quality, and can possibly reveal pathologies previously obscured by artifacts, without additional dose application. KEY POINTS: • Photon-counting detector CT (PCD-CT) offers highly effective approaches for metal artifact reduction in patients with dental fillings/implants. • Iterative metal artifact reduction (iMAR) is superior to high keV monoenergetic reconstructions at 140 keV for artifact reduction and provides higher image quality. • Signal homogeneity of the reconstructed images is not affected by the different artifact reduction techniques.

Phantom-based radiomics feature test-retest stability analysis on photon-counting detector CT.

OBJECTIVES: Radiomics image data analysis offers promising approaches in research but has not been implemented in clinical practice yet, partly due to the instability of many parameters. The aim of this study is to evaluate the stability of radiomics analysis on phantom scans with photon-counting detector CT (PCCT). METHODS: Photon-counting CT scans of organic phantoms consisting of 4 apples, kiwis, limes, and onions each were performed at 10 mAs, 50 mAs, and 100 mAs with 120-kV tube current. The phantoms were segmented semi-automatically and original radiomics parameters were extracted. This was followed by statistical analysis including concordance correlation coefficients (CCC), intraclass correlation coefficients (ICC), as well as random forest (RF) analysis, and cluster analysis to determine the stable and important parameters. RESULTS: Seventy-three of the 104 (70%) extracted features showed excellent stability with a CCC value > 0.9 when compared in a test and retest analysis, and 68 features (65.4%) were stable compared to the original in a rescan after repositioning. Between the test scans with different mAs values, 78 (75%) features were rated with excellent stability. Eight radiomics features were identified that had an ICC value greater than 0.75 in at least 3 of 4 groups when comparing the different phantoms in a phantom group. In addition, the RF analysis identified many features that are important for distinguishing the phantom groups. CONCLUSION: Radiomics analysis using PCCT data provides high feature stability on organic phantoms, which may facilitate the implementation of radiomics analysis likewise in clinical routine. KEY POINTS: • Radiomics analysis using photon-counting computed tomography provides high feature stability. • Photon-counting computed tomography may pave the way for implementation of radiomics analysis in clinical routine.

Photon-Counting Computed Tomography (PC-CT) of the spine: impact on diagnostic confidence and radiation dose.

OBJECTIVES: Computed tomography (CT) is employed to evaluate surgical outcome after spinal interventions. Here, we investigate the potential of multispectral photon-counting computed tomography (PC-CT) on image quality, diagnostic confidence, and radiation dose compared to an energy-integrating CT (EID-CT). METHODS: In this prospective study, 32 patients underwent PC-CT of the spine. Data was reconstructed in two ways: (1) standard bone kernel with 65-keV (PC-CTstd) and (2) 130-keV monoenergetic images (PC-CT130 keV). Prior EID-CT was available for 17 patients; for the remaining 15, an age-, sex-, and body mass index-matched EID-CT cohort was identified. Image quality (5-point Likert scales on overall, sharpness, artifacts, noise, diagnostic confidence) of PC-CTstd and EID-CT was assessed by four radiologists independently. If metallic implants were present (n = 10), PC-CTstd and PC-CT130 keV images were again assessed by 5-point Likert scales by the same radiologists. Hounsfield units (HU) were measured within metallic artifact and compared between PC-CTstd and PC-CT130 keV. Finally, the radiation dose (CTDIvol) was evaluated. RESULTS: Sharpness was rated significantly higher (p = 0.009) and noise significantly lower (p < 0.001) in PC-CTstd vs. EID-CT. In the subset of patients with metallic implants, reading scores for PC-CT130 keV revealed superior ratings vs. PC-CTstd for image quality, artifacts, noise, and diagnostic confidence (all p < 0.001) accompanied by a significant increase of HU values within the artifact (p < 0.001). Radiation dose was significantly lower for PC-CT vs. EID-CT (mean CTDIvol: 8.83 vs. 15.7 mGy; p < 0.001). CONCLUSIONS: PC-CT of the spine with high-kiloelectronvolt reconstructions provides sharper images, higher diagnostic confidence, and lower radiation dose in patients with metallic implants. KEY POINTS: • Compared to energy-integrating CT, photon-counting CT of the spine had significantly higher sharpness and lower image noise while radiation dose was reduced by 45%. • In patients with metallic implants, virtual monochromatic photon-counting images at 130 keV were superior to standard reconstruction at 65 keV in terms of image quality, artifacts, noise, and diagnostic confidence.

Low dose pediatric chest computed tomography on a photon counting detector system - initial clinical experience.

BACKGROUND: With the clinical release of a photon counting detector-based computed tomography (CT) system, the potential benefits of this new technology need to be evaluated clinically. Literature concerning this new generation of detector is sparse, especially in the field of pediatric radiology. Therefore, this study outlines our initial experience with ultra-low dose chest CT imaging on the new photon counting CT system. MATERIALS AND METHODS: A pediatric phantom (1-year old, CIRS ATOM phantom, model 704 [CIRS-computerized imaging reference system, Norfolk, VA]) was scanned at different dose levels and different image quality levels to define a protocol for clinical examinations. Next, 20 consecutive pediatric non-contrast ultra-low dose chest CT examinations were evaluated for radiation dose and diagnostic image quality using a 4-point Likert-scale-1 = excellent, 4 = bad image quality-by two radiologists in a consensus reading. This retrospective analysis was approved by the local research ethics committee. RESULTS: Chest CT examinations performed at ultra-low radiation dose (effective dose 0.19 ± 0.07 mSv; size-specific dose estimate 0.45 ± 0.14 mGy) in pediatric patients ages (2.6 ± 1.8 years) show good to excellent image quality for lung structures (1.4 ± 0.4) and moderate image quality for soft tissue structures (2.8 ± 0.2). CONCLUSION: Pediatric ultra-low dose chest CT examinations are feasible with the new generation photon counting detector-based CT system. The benefits of this technology must be evaluated for pediatric patients from the outset.

Age-related outcome of facial reanimation surgery using cross face nerve graft and gracilis free functional muscle transfer-A retrospective cohort study.

BACKGROUND: Free functional muscle transfer has become the criterion standard for the treatment of long-standing flaccid facial paralysis. Clinical experience suggests that a two-stage approach using a cross-face nerve graft (CFNG) as a donor nerve for free functional muscle transfers (FFMT) is less successful in older patients when compared to the pediatric population. However, clear data and scientific evidence are still rare. This study examines the age-related outcome of CFNG-driven FFMT. METHODS: Twenty-eight patients with a mean age of 20.73 years (ranging 5-51 years) who received two-stage facial reanimation with CFNG-driven gracilis FFMT at our institution from 1998 to 2019 were included. The ipsilateral sural nerve was used as CFNG. After 12 months, the ipsilateral gracilis muscle was used as FFMT. Patients were distributed equally into three cohorts according to their age. We assessed facial symmetry before and after facial reanimation measuring the angle between the interpupillary and the intermodiolar line (pupillo-modiolar angle). Additionally, the commissure height was measured using the Emotrics software. RESULTS: The mean follow-up of the pediatric, young adults and the middle-aged cohort was 29.5 ± 7.3, 24.9 ± 6.3, and 25.5 ± 12.4 months, respectively. One patient suffered flap loss due to flap ischemia. Four patients suffered insufficient innervation of the FFMT. Otherwise no major complication occurred. The likelihood of successful innervation of the FFMT was significantly higher in patients younger than 31 years (100% vs. 50%; p = .003). Smiling facial symmetry (pupillo-modiolar angle) significantly improved in the pediatric cohort (5-16 years; 8.68° ± 0.69° to 1.48° ± 0.67°; p < .001) and the young adults' cohort (17-30 years; 11.55° ± 1.95° to 4.62° ± 1.08°; p = .005), but improved only slightly in the middle-aged cohort (31-51 years; 11.77° ± 1.16° to 9.4° ± 1.8° p = .27). The postoperative smiling symmetry showed a significant correlation with increasing age (r = .62, p < .001). The smiling commissure height deviation significantly improved in the pediatric cohort (5-16 years; 6.5-2.3 mm; p = .006) and the postoperative result was significantly better than the middle-aged group (31-51 years; 2.3 vs. 7.5 mm; p = .02). CONCLUSIONS: The outcome of CFNG-driven gracilis FFMT is age-related. Static as well as dynamic facial symmetry after two-stage facial reanimation was best in the pediatric and young adult population. For older patients, other approaches like the nerve-to-masseter-driven FFMT should be considered.

MR-guided microwave ablation in hepatic malignancies: clinical experiences from 50 procedures.

Purpose: To investigate technical success, technique efficacy, safety and outcome of MR-guided microwave ablation (MWA) in hepatic malignancies.Material and methods: In this prospective IRB-approved study, patients scheduled for percutaneous treatment of hepatic malignancies underwent MR-guided MWA in a closed-bore 1.5 T MR system. Technical success was assessed on post-procedural MR control imaging. Technique efficacy was evaluated 4 weeks after the procedure on multi-parametric MRI. Assessment of safety followed the Society of Interventional Radiology grading system. Kaplan-Meier survival estimates were calculated to evaluate overall survival (OS), time to local tumor progression (TLTP), and time to non-target progression (TNTP).Results: Between 2015 and 2019, 47 patients (60.5 ± 12.2 years; 39 male) underwent 50 procedures for 58 hepatic tumors (21 hepatocellular carcinomas; 37 metastases). Mean target tumor size was 16 ± 7mm (range: 6-39 mm). Technical success and technique efficacy were 100% and 98%, respectively. Lesions were treated using 2.6 applicator positions (range: 1-6). Mean energy, ablation duration per tumor, and procedure duration were 43.2 ± 23.5 kJ, 26.7 ± 13.1 min and 211.2 ± 68.7 min, respectively. 10 minor (20%) and 3 major (6%) complications were observed. Median post-interventional hospital admission was 1 day (range: 1-19 days). Median OS was 41.6 (IQR: 26.4-) months. Local recurrence occurred after 4 procedures (8%) with TLTP ranging between 3.1 and 41.9 months. Non-target recurrence was observed in 64% of patients after a median TNTP of 13.8 (IQR 2.3-) months.Conclusion: MR-guided MWA allows for safe and successful treatment of hepatic malignancies with a high technique efficacy however with relatively long procedure durations.

Feasibility, efficacy, and safety of percutaneous MR-guided ablation of small (≤12 mm) hepatic malignancies.

BACKGROUND: Percutaneous tumor ablation is commonly performed using computed tomography (CT) or ultrasound (US) guidance, although reliable visualization of the target tumor may be challenging. MRI guidance provides more reliable visualization of target tumors and allows for real-time imaging and multiplanar capabilities, making it the modality of choice, in particular if lesions are small. PURPOSE: To investigate the feasibility, technical success, and safety of percutaneous MR-guided ablation (RFA n = 27 / MWA n = 16) of small (≤12 mm) hepatic malignancies. STUDY TYPE: Retrospective case study. POPULATION: In all, 45 patients (age: 61.1 ± 11.8) with hepatic malignancies and a lesion diameter of ≤12 mm scheduled for percutaneous MR-guided tumor ablation based on a tumor board decision were included. FIELD STRENGTH: A 1.5T MR system was used for planning, targeting, and monitoring. ASSESSMENT: Feasibility assessment included the detection of the target tumor, tumor delineation during MR-fluoroscopy guided targeting, and the number of attempts needed for precise applicator placement. Technical success was defined as successful performance of the procedure including a safety margin of 5 mm. Safety evaluation was based on procedure-related complications. STATISTICAL TEST: Frequency. RESULTS: Tumor ablation (mean diameter 9.0 ± 2.1 mm) was successfully completed in 43/45 patients. Planning imaging was conducted without a contrast agent in 79% (n = 37). In 64% (n = 30), the target tumors were visible with MR-fluoroscopy. In six patients (13%), planning imaging revealed new, unexpected small lesions, which were either treated in the same session (n = 4) or changed therapy management (n = 2) due to diffuse tumor progress. Postprocedural imaging revealed a technical success of 100% (43/43), with no major complications. During follow-up, no local tumor progression was observed (mean follow-up 24.7 ± 14.0 months) although 28% (12) patients developed new hepatic lesions distant to the ablation zone. No major complications were observed. DATA CONCLUSION: MR-guided ablation is a feasible approach for an effective and safe treatment of small hepatic malignancies. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;49:374-381.

Reduced scan range abdominopelvic CT in patients with suspected acute appendicitis - impact on diagnostic accuracy and effective radiation dose.

BACKGROUND: To evaluate a reduced range CT protocol in patients with suspected acute appendicitis as compared to standard abdominal CT regarding diagnostic performance, effective radiation dose and organ doses. METHODS: In this study, we retrospectively included 90 patients (43 female, mean age 56.7 ± 17 years) with suspected acute appendicitis who underwent CT of abdomen and pelvis. From those CTs, we reconstructed images with a reduced scan range from L1 to the the pubic symphysis. Full range and reduced range datasets were assessed by two radiologists for i) coverage of the Appendix, ii) presence/absence of appendicitis and iii) presence of differential diagnoses. Furthermore, effective radiation doses as well as organ doses were calculated using a commercially available dose management platform (Radimetrics, Bayer HealthCare). RESULTS: The Appendix was covered by the reduced range CT in all cases. In 66 patients CT confirmed the presence of appendicitis. In 14 patients, other relevant differential diagnoses were identified by CT, whereas in 10 patients no relevant findings were detected. Both readers identified all patients with appendicitis on both full and reduced range CT. For reduced range CT, total effective dose was 39% lower than for full range CT (reduced range: 4.5 [1.9-11.2] vs. full range: 7.4 [3.3-18.8] mSv; p ≤ 0.001). Notably, a remarkable reduction of organ dose in the female breasts by 97% (0.1 [0.1-0.6] vs. 3.8 [0.5-18.8] mSv; p ≤ 0.001) and in the testicles in males by 81% (3.4 [0.7-32.7] vs. 17.6 [5.4-52.9] mSv; p ≤ 0.001) was observed for reduced range CT compared to full range CT. CONCLUSIONS: In patients with suspected acute appendicitis, reduced range abdominopelvic CT results in a comparable diagnostic performance with a remarkable reduction of total effective radiation dose and organ doses (especially breast dose in female and testicle dose in male patients) as compared to full range CT.

Voxel-wise correlation of functional imaging parameters in HNSCC patients receiving PET/MRI in an irradiation setup.

PURPOSE: The purpose of this study was to demonstrate the feasibility of voxel-wise multiparametric characterization of head and neck squamous cell carcinomas (HNSCC) using hybrid multiparametric magnetic resonance imaging and positron emission tomography with [18F]-fluorodesoxyglucose (FDG-PET/MRI) in a radiation treatment planning setup. METHODS: Ten patients with locally advanced HNSCC were examined with a combined FDG-PET/MRI in an irradiation planning setup. The multiparametric imaging protocol consisted of FDG-PET, T2-weighted transverse short tau inversion recovery sequence (STIR) and diffusion-weighted MRI (DWI). Primary tumours were manually segmented and quantitative imaging parameters were extracted. PET standardized uptake values (SUV) and DWI apparent diffusion coefficients (ADC) were correlated on a voxel-wise level. RESULTS: Images acquired in this specialised radiotherapy planning setup achieved good diagnostic quality. Median tumour volume was 4.9 [1.1-42.1] ml. Mean PET SUV and ADC of the primary tumours were 5 ± 2.5 and 1.2 ± 0.3 10-3 mm2/s, respectively. In voxel-wise correlation between ADC values and corresponding FDG SUV of the tumours, a significant negative correlation was observed (r = -0.31 ± 0.27, p < 0.05). CONCLUSION: Multiparametric voxel-wise characterization of HNSCC is feasible using combined PET/MRI in a radiation planning setup. This technique may provide novel insights into tumour biology with regard to radiation therapy in the future.

Self-gated 4D-MRI of the liver: Initial clinical results of continuous multiphase imaging of hepatic enhancement.

PURPOSE: To evaluate the feasibility of a self-gated free-breathing volume-interpolated breath-hold examination (VIBE) sequence using compressed sensing (CS) for contrast-enhanced multiphase liver MRI. MATERIALS AND METHODS: We identified 23 patients who underwent multiphase gadobutrol-enhanced liver magnetic resonance imaging (MRI) using 1) a prototype free-breathing VIBE sequence with respiratory self-gating and CS (VIBECS ), and 2) a standard breath-hold VIBE (VIBESTD ) on the same 1.5T scanner at two timepoints. VIBECS was continuously acquired for 128 seconds and a time-series of 16 timepoints was jointly reconstructed from the dataset. The unenhanced, arterial, portal-venous, and venous timepoints with the best image quality were selected and compared to the corresponding VIBESTD series serving as reference. Image quality was assessed qualitatively (image quality, sharpness, lesion conspicuity, vessel contrast, noise, motion/other artifacts; two readers independently; 5-point Likert scale; 5 = excellent) and quantitatively (vessel contrast [VC], coefficient-of-variation [CV]) Statistics were performed using Wilcoxon-sign-rank (ordinal) and paired t-test (continuous variables). RESULTS: Image quality and lesion conspicuity revealed no significant differences between the sequences (P ≥ 0.3). VIBESTD showed a tendency to higher motion artifacts (P ≥ 0.07). Image sharpness significantly increased in VIBECS as compared to VIBESTD (P ≤ 0.03). Arterial phase vessel contrast appeared significantly lower in VIBECS than in VIBESTD (P = 0.04). VIBECS showed reconstruction artifacts not present in VIBESTD (P = 0.001). Image noise was significantly lower in VIBECS than in VIBESTD (P ≤ 0.004). Arterial phase VC was significantly lower in VIBECS than in VIBESTD (P = 0.01). CV revealed no differences between sequences (P = 0.7). CONCLUSION: VIBECS is feasible for continuous free-breathing contrast-enhanced multiphase liver MRI, providing similar image quality and lesion conspicuity as VIBESTD . LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:459-467.

Scan time reduction in diffusion-weighted imaging of the pancreas using a simultaneous multislice technique with different acceleration factors: How fast can we go?

OBJECTIVES: To investigate the feasibility of simultaneous multislice-accelerated diffusion-weighted imaging (sms-DWI) of the pancreas with different acceleration factors and its influence on image quality, acquisition time and apparent diffusion coefficients (ADCs) in comparison to conventional sequences. METHODS: DWI of the pancreas was performed at 1.5T in ten healthy volunteers and 20 patients with sms-accelerated echo-planar DWI using two different sms-acceleration factors of 2 and 3 (sms2/3-DWI). These DWI sequences were compared to conventional DWI (c-DWI) in terms of image quality parameters (5-point Likert scale) and ADC measurements. RESULTS: c-DWI and sms2-DWI offered equivalently high overall image quality (4 [1; 5]) with scan time reduction to one-third (c-DWI: 173 s, sms2-DWI: 56 s). Sms3-DWI showed significantly poorer overall image quality (3 [1; 5]; p < 0.0001). ADC values were significantly lower in sms3-DWI compared to c-DWI in the pancreatic body and tail (body: c-DWI 1.4 x 10-3 mm2/s, sms3-DWI 1.0 x 10-3 mm2/s, p = 0.028; tail: c-DWI 1.3 x 10-3 mm2/s and sms3-DWI 1.0 x 10-3 mm2/s, p = 0.014). CONCLUSIONS: Accelerated multislice DWI of the pancreas offers high image quality with a substantial reduction of acquisition time. Lower ADC values in multislice DWI should be considered in diagnostic reading. KEY POINTS: • Simultaneous multislice-accelerated diffusion-weighted imaging (sms-DWI) promises scan time minimisation. • Sms-DWI of the pancreas offers diagnostic image quality in volunteers and patients. • Sms-DWI with an acceleration factor of 2 offers high image quality. • Higher acceleration factors in sms-DWI do not provide sufficient diagnostic image quality. • ADC values may be lower in sms-DWI.

Impact of dual-energy CT post-processing to differentiate venous thrombosis from iodine flux artefacts.

OBJECTIVES: To investigate the accuracy of dual-energy (DE) CT-based iodine maps (IM) and noise-optimised monoenergetic extrapolations (MEI+) at 40 keV for the detection and differentiation of venous thrombosis (VT) from iodine flux artefacts (IFA) in comparison to portal-venous phase CT (CTPV). METHODS: Ninety-nine patients were enrolled in this study. In all patients, VT or IFA was suspected on contrast-enhanced CT and confirmed by follow-up CT or colour-coded ultrasound. All examinations were performed on a third-generation dual-source CT system in DE mode during portal-venous phase. CTPV, IM and 40-keV MEI+ were reconstructed and independently evaluated by two radiologists for the presence/absence of VT and/or IFA. Diagnostic confidence was rated on a three-point scale (3 = high confidence). Quantitative parameters were obtained by calculating contrast-to-noise ratios (CNRs), iodine content and thrombus volume. Diagnostic accuracy was assessed by calculating receiver operating characteristics (ROC) of CNR. RESULTS: Diagnostic confidence was significantly higher for IM and MEI+ [both 3 (2-3)] compared to CTPV [2 (1-3); p ≤ 0.03]. ROC analysis revealed significantly higher AUC values and increased sensitivity for IM and MEI+ (AUC = 88%/sensitivity = 79.1% and 86%/73.1%) than for CTPV (75%/61.2%; p ≤ 0.01). Thrombus volume was significantly higher in MEI+ than in IM and CTPV (p < 0.001). CNR of thrombosis was significantly higher in IM [11.5 (8.5-14.5), p < 0.001) and MEI+ [10.9 (8.8-15.5), p < 0.001] than in CTPV [8.2 (5.8-11.4)]. Iodine quantification revealed significantly lower results in VT than in IFA [0.55 mg/ml (0.23-0.90) and 1.81 (1.60-2.12) mg/ml; p < 0.001]. CONCLUSIONS: IM and MEI+ 40 keV showed significantly higher diagnostic confidence and accuracy for the detection and differentiation of VT from IFA in comparison to CTPV. KEY POINTS: • Iodine maps and noise-optimised monoenergetic extrapolations at 40 keV increase diagnostic confidence and accuracy for the detection and differentiation of venous thrombosis from iodine flux artefacts. • Dual-energy post-processing can significantly increase contrast-to-noise ratio and the sensitivity for the diagnosis of venous thrombosis • Iodine load in venous thrombosis is significantly lower than in iodine flux artefacts.