Quantitative differentiation of minimal-fat angiomyolipomas from renal cell carcinomas using grating-based x-ray phase-contrast computed tomography: An ex vivo study.

BACKGROUND: The differentiation of minimal-fat-or low-fat-angiomyolipomas from other renal lesions is clinically challenging in conventional computed tomography. In this work, we have assessed the potential of grating-based x-ray phase-contrast computed tomography (GBPC-CT) for visualization and quantitative differentiation of minimal-fat angiomyolipomas (mfAMLs) and oncocytomas from renal cell carcinomas (RCCs) on ex vivo renal samples. MATERIALS AND METHODS: Laboratory GBPC-CT was performed at 40 kVp on 28 ex vivo kidney specimens including five angiomyolipomas with three minimal-fat (mfAMLs) and two high-fat (hfAMLs) subtypes as well as three oncocytomas and 20 RCCs with eight clear cell (ccRCCs), seven papillary (pRCCs) and five chromophobe RCC (chrRCC) subtypes. Quantitative values of conventional Hounsfield units (HU) and phase-contrast Hounsfield units (HUp) were determined and histogram analysis was performed on GBPC-CT and grating-based attenuation-contrast computed tomography (GBAC-CT) slices for each specimen. For comparison, the same specimens were imaged at a 3T magnetic resonance imaging (MRI) scanner. RESULTS: We have successfully matched GBPC-CT images with clinical MRI and histology, as GBPC-CT presented with increased soft tissue contrast compared to absorption-based images. GBPC-CT images revealed a qualitative and quantitative difference between mfAML samples (58±4 HUp) and oncocytomas (44±10 HUp, p = 0.057) and RCCs (ccRCCs: 40±12 HUp, p = 0.012; pRCCs: 43±9 HUp, p = 0.017; chrRCCs: 40±7 HUp, p = 0.057) in contrast to corresponding laboratory attenuation-contrast CT and clinical MRI, although not all differences were statistically significant. Due to the heterogeneity and lower signal of oncocytomas, quantitative differentiation of the samples based on HUp or in combination with HUs was not possible. CONCLUSIONS: GBPC-CT allows quantitative differentiation of minimal-fat angiomyolipomas from pRCCs and ccRCCs in contrast to absorption-based imaging and clinical MRI.

Assessment of MRI-Detected Breast Lesions: A Benign Correlate on Second-Look Ultrasound Can Safely Exclude Malignancy.

INTRODUCTION: Due to the increasing use of dynamic breast MRI and the limited availability of MR-guided interventions, MRI-detected lesions usually undergo a second-look ultrasound (SLUS). We investigated the safety of a negative SLUS and a benign SLUS correlate in excluding malignant and high-risk lesions (B3) and evaluated criteria for the rate of detection on SLUS. METHODS: In the retrospective analysis, all breast MRIs performed between 2011 and 2013 were screened for newly detected lesions. We analyzed the SLUS detection rate dependent on breast density, mass character, lesion size, and histology. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of a negative and benign SLUS for malignant lesions (B5) and lesions requiring surgical excision (including high-risk and B5 lesions). RESULTS: We successfully correlated 110 of 397 lesions. The detection rate was significantly higher for mass than for non-mass lesions and correlated with lesion size for mass lesions only. Lesions without/with a benign SLUS correlate were more frequently benign (including B3) or required no further procedure (B2). The sensitivity of SLUS in the detection of B3 and B5 lesions was 58%, and 73% in the detection of B5 lesions. The NPV of a negative or benign SLUS for B3 and B5 lesions was 89%, and 96% for B5 lesions. DISCUSSION: SLUS is a safe diagnostic tool for the management of MRI-detected lesions and can spare patients from undergoing invasive procedures.

Infrared molecular fingerprinting of blood-based liquid biopsies for the detection of cancer.

Recent omics analyses of human biofluids provide opportunities to probe selected species of biomolecules for disease diagnostics. Fourier-transform infrared (FTIR) spectroscopy investigates the full repertoire of molecular species within a sample at once. Here, we present a multi-institutional study in which we analysed infrared fingerprints of plasma and serum samples from 1639 individuals with different solid tumours and carefully matched symptomatic and non-symptomatic reference individuals. Focusing on breast, bladder, prostate, and lung cancer, we find that infrared molecular fingerprinting is capable of detecting cancer: training a support vector machine algorithm allowed us to obtain binary classification performance in the range of 0.78-0.89 (area under the receiver operating characteristic curve [AUC]), with a clear correlation between AUC and tumour load. Intriguingly, we find that the spectral signatures differ between different cancer types. This study lays the foundation for high-throughput onco-IR-phenotyping of four common cancers, providing a cost-effective, complementary analytical tool for disease recognition.

Visualization of the epimysium and fascia thoracolumbalis at the lumbar spine using MRI.

BACKGROUND: The fascia thoracolumbalis (FTL) is an important component for stabilization and motion control of the lumbar spine. It coordinates the traction forces of the autochthonous muscles of the back (AM) and connects them to the muscles of the abdominal wall, shoulder, and buttocks. OBJECTIVES: The aim of our study was to describe the assessment of the normal FTL and epimysium of the AM in MRI and to identify patterns associated with pathological changes in the lumbar spine. MATERIAL AND METHODS: A total of 33 patients were retrospectively evaluated: 15 patients had no pathology at the lumbar spine; six patients had previous hemilaminectomy, three had spondylodesis, two had ventrolisthesis, and seven had scoliosis. The thickness of the FTL and EM was measured, and the adhesion of both structures was assessed. RESULTS: The fascial thickness at the levels of the lumbar vertebral bodies LVB 3 was 1.8, of LVB 4 it was 2.0, of LVB 5 it was 2.1, and at the sacral vertebra SVB 1 it was 1.8 mm. Fascial adhesions together with thickening of the EM occurred at the level of LVB 4 in 36% of the cases independently of the underlying disorder. Only thickening of the EM was seen in 48% of cases at the level of SVB 1. By contrast, adhesion of the FTL without epimysial changes occurred in 36% of cases at the level of LVB 3. CONCLUSION: Thickening and adhesions at the EM and FTL occurred both postoperatively and in the case of scoliosis. Furthermore, lipomatous and muscular herniation could be detected in the FTL postoperatively. Epimysial and fascial alterations may be imaging manifestations of chronic myofascial back pain and should be included in radiological assessments.

Is bone marrow edema syndrome a precursor of hip or knee osteonecrosis? Results of 49 patients and review of the literature.

PURPOSE: Diagnosis of bone marrow edema syndrome (BMES) can be challenging. There is sometimes uncertainty about the correct diagnosis of BMES on morphologic magnetic resonance imaging (MRI), since subchondral findings like lines and spots can be misinterpreted as "beginning" or "possible" avascular osteonecrosis (AVN). The aim of our study was to systematically assess the temporal course of BMES from first diagnosis on MRI until the end of clinical symptoms and the full disappearance of bone marrow edema (BME) to determine whether subchondral lines and spots detected in these patients can develop into osteonecrosis. METHODS: In a combined retrospective and prospective study, we retrieved serial MRI scans of hips and knees with BME from the hospital database. According to clinical and imaging data, all patients with degenerative, infectious/inflammatory, rheumatic, neoplastic conditions and those showing typical osteonecrosis were excluded. We collected all available MRI examinations from first detection of BME until its disappearance. In case edema had not fully resolved in the last available MRI scan, we performed an MRI with an additional dynamic contrast-enhanced (DCE-MRI) sequence. For each MRI scan, we recorded the severity of edema, the presence of subchondral hypointense lines and the presence of subchondral focal hypointense zones on T1-weighted images by two independent readers. The DCE-MRI scans were used to calculate parameter maps to assess the perfusion characteristics. RESULTS: The study comprised 49 patients aged 22-71 years. In total, 171 morphologic and 5 DCE-MRI scans were evaluated. In 44 patients (89.8%), the BMES completely healed without remnants. In 18 of 49 patients (36.7%), a subchondral line was present in the first MRI exam. Nine patients (18.4%) developed a subchondral line within 1-5 months after the first MRI. In total, 27 out of 49 patients (55.1%) had subchondral lines (12 knees, 15 hips) during the timeframe of the study. All subchondral lines disappeared in the timeframe of the study. Subchondral focal hypointense zones were present in 14 out of 49 patients (28.6%): in 9 cases, subchondral focal hypointense zones disappeared after a median of 5.5 months (range, 1-85 months), while in 5 cases, subchondral focal lesions persisted until the end of the study (up to more than 85 months) without edema in the surrounding bone. All persisting subchondral focal lesions were hyperperfused. These 5 patients had associated meniscal lesions. CONCLUSION: Our study shows that subchondral lines and spots found in patients with BMES do not develop into AVN. Subchondral lines, which resemble subchondral insufficiency fractures, are associated with BMES. Subchondral focal T1-hypointense zones do not represent AVN; most probably these areas represent reparative processes within the subchondral bone, where tensile and shear force overload is present due to altered biomechanics.

Papillary vs clear cell renal cell carcinoma. Differentiation and grading by iodine concentration using DECT-correlation with microvascular density.

OBJECTIVES: Various imaging methods have been evaluated regarding non-invasive differentiation of renal cell carcinoma (RCC) subtypes. Dual-energy computed tomography (DECT) allows iodine concentration (IC) analysis as a correlate of tissue perfusion. Microvascular density (MVD) in histopathology specimens is evaluated to determine intratumoral vascularization. The objective of this study was to assess the potential of IC and MVD regarding the differentiation between papillary and clear cell RCC and between well- and dedifferentiated tumors. Further, we aimed to investigate a possible correlation between these parameters. METHODS: DECT imaging series of 53 patients with clear cell RCC (ccRCC) and 15 with papillary RCC (pRCC) were analyzed regarding IC. Histology samples were stained using CD31/CD34 monoclonal antibodies; MVD was evaluated digitally. Statistical analysis included performance of Mann-Whitney U test, ROC analysis, and Spearman rank correlation. RESULTS: Analysis of IC demonstrated significant differences between ccRCC and pRCC (p < 0.001). A cutoff value of ≤ 3.1 mg/ml at IC analysis allowed identification of pRCC with an accuracy of 86.8%. Within the ccRCC subgroup, G1/G2 tumors could significantly be differentiated from G3/G4 carcinomas (p = 0.045). A significant positive correlation between IC and MVD could be determined for the entire RCC cohort and the ccRCC subgroup. Limitations include the small percentage of pRCCs. CONCLUSIONS: IC analysis is a useful method to differentiate pRCC from ccRCC. The significant positive correlation between IC and MVD indicates valid representation of tumor perfusion by DECT. KEY POINTS: • Analysis of iodine concentration using DECT imaging could reliably distinguish papillary from clear cell subtypes of renal cell cancer (RCC). • A cutoff value of 3.1 mg/ml allowed a distinction between papillary and clear cell RCCs with an accuracy of 86.8%. • The positive correlation with microvascular density in tumor specimens indicates correct display of perfusion by iodine concentration analysis.

CT Fluoroscopy-Guided Drain Placement to Treat Infected Gastric Leakage after Sleeve Gastrectomy: Technical and Clinical Outcome of 31 Procedures.

PURPOSE: To observe the technical and clinical outcome as well as safety of CT fluoroscopy-guided drain placement in the multimodal clinical complication management of superinfected gastric leakage after sleeve gastrectomy. MATERIALS AND METHODS: All consecutive patients who underwent CT fluoroscopy-guided drain placement to treat superinfected postoperative leakage after sleeve gastrectomy in our department between 2007 and 2014 were included in this retrospective study. All interventions were performed on a 16- or 128-row CT scanner under intermittent CT fluoroscopy guidance (15-25 mAs, 120 kV). The technical and clinical success rates as well as complications, additional therapies and patient radiation dose were analyzed. RESULTS: 14 patients (mean age: 43.8 ±â€Š11.3 years, mean BMI: 52.9 ±â€Š13.5, 7 women) who underwent a total of 31 CT fluoroscopy-guided drain placement procedures were included. 30 of 31 interventions (96.8 %) were technically successful. 7 patients underwent more than one intervention due to drain obstruction or secondary dislocation or as further treatment. During and after the intervention no procedure-associated complications occurred. In all patients, inflammation parameters decreased within days after the CT-guided intervention. The total interventional dose length product (DLP) was 1561 ±â€Š1035 mGy*cm. CONCLUSION: CT fluoroscopy-guided drain placement has been shown to be a safe minimally invasive procedure that rarely leads to complications for treating superinfected gastric leakage occurring after sleeve gastrectomy. We assume that operative revisions in a high-risk patient group can be avoided using this procedure. KEY POINTS: · CT fluoroscopy-guided drain placement in obese - often medically highly complex - patients is a technically feasible procedure.. · Multimodal treatment (CT intervention, endoscopy and surgery) is required to successfully treat gastric leakage after bariatric surgery.. · High-risk surgery might be avoided by the CT-guided drain placement.. CITATION FORMAT: · Schwarz J, Strobl FF, Paprottka PM et al. CT Fluoroscopy-Guided Drain Placement to Treat Infected Gastric Leakage after Sleeve Gastrectomy: Technical and Clinical Outcome of 31 Procedures. Fortschr Röntgenstr 2020; 192: 163 - 170.

Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects.

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants' smoking and sporting habits were measured by a questionnaire. Physical inactivity was associated with a reduction of left ventricular ejection fraction (LV-EF), stroke volume, early diastolic peak filling rate and peak ejection rate of the left ventricle as well as right ventricular stroke volume. LV-EF was reduced in subjects with almost no physical activity compared to subjects with regular physical activity (68.4%, 95%CI 66.8-70.1% vs. 70.8%, 95%CI 69.2-72.3%, p < 0,05). Smokers had lower right ventricular end-diastolic volumes (80.6 ml/m², 95%CI 76.7-84.5 ml/m²; never-smokers: 85.5 ml/m², 95%CI 82.6-88.3 ml/m²; p < 0.05) but higher extracellular volume fractions (ECV) and fibrosis volumes (34.3 ml, 95%CI 32.5-36.0 ml, vs. 31.0 ml, 95%CI 29.6-32.3 ml, p < 0.01). We conclude that asymptomatic individuals without known cardiovascular diseases show differences in cardiac function and structure depending on their physical activity and smoking habits. This underlines the importance of prevention and health education.

Radiation dose and image quality of high-pitch emergency abdominal CT in obese patients using third-generation dual-source CT (DSCT).

In this third-generation dual-source CT (DSCT) study, we retrospectively investigated radiation dose and image quality of portal-venous high-pitch emergency CT in 60 patients (28 female, mean age 56 years) with a body mass index (BMI) ≥ 30 kg/m2. Patients were dichotomized in groups A (median BMI 31.5 kg/m2; n = 33) and B (36.8 kg/m2; n = 27). Volumetric CT dose index (CTDIvol), size-specific dose estimate (SSDE), dose length product (DLP) and effective dose (ED) were assessed. Contrast-to-noise ratio (CNR) and dose-independent figure-of-merit (FOM) CNR were calculated. Subjective image quality was assessed using a five-point scale. Mean values of CTDIvol, SSDE as well as normalized DLP and ED were 7.6 ± 1.8 mGy, 8.0 ± 1.8 mGy, 304 ± 74 mGy * cm and 5.2 ± 1.3 mSv for group A, and 12.6 ± 3.7 mGy, 11.0 ± 2.6 mGy, 521 ± 157 mGy * cm and 8.9 ± 2.7 mSv for group B (p < 0.001). CNR of the liver and spleen as well as each calculated FOM CNR were significantly higher in group A (p < 0.001). Subjective image quality was good in both groups. In conclusion, third-generation abdominal high-pitch emergency DSCT yields good image quality in obese patients. Radiation dose increases in patients with a BMI > 36.8 kg/m2.

Retrospective outcome analysis of rates and types of complications after 8654 minimally invasive radiological port implantations via the subclavian vein without ultrasound guidance.

PURPOSE: To evaluate the rate and types of complications after minimally invasive radiological central vein port implantation without ultrasound guidance. MATERIALS AND METHODS: We retrospectively evaluated 8654 patients who underwent port implantations in the subclavian vein without ultrasound guidance in our institution from 1998 to 2014 with regard to types and rates of peri-, early and late post-interventional complications according to the common classification for complications published by the Society of Interventional Radiology (SIR). Additionally, the impact of the training level of the operators on the rate of complications was analyzed. RESULTS: Successful port implantations were performed in 99.8% (8636/8654 procedures). From 1998 to 2014, a total of 565 (6.52%) complications were recorded. The overall percentage of the peri-, early and late post-interventional complications according to the SIR criteria was 1.69, 0.15 and 4.68, respectively. Significant differences due to the training level of the performing physician could be seen for the rates of pneumothorax, arterial puncture and hematoma. CONCLUSION: Minimally invasive radiological interventional port implantation is a safe treatment option with a low rate of complications even without ultrasound guidance.

Assessment of intraductal carcinoma in situ (DCIS) using grating-based X-ray phase-contrast CT at conventional X-ray sources: An experimental ex-vivo study.

BACKGROUND: The extent of intraductal carcinoma in situ (DCIS) is commonly underestimated due to the discontinuous growth and lack of microcalcifications. Specimen radiography has been established to reduce the rate of re-excision. However, the predictive value for margin assessment with conventional specimen radiography for DCIS is low. In this study we assessed the potential of grating-based phase-contrast computed tomography (GBPC-CT) at conventional X-ray sources for specimen tomography of DCIS containing samples. MATERIALS AND METHODS: GBPC-CT was performed on four ex-vivo breast specimens containing DCIS and invasive carcinoma of non-specific type. Phase-contrast and absorption-based datasets were manually matched with corresponding histological slices as the standard of reference. RESULTS: Matching of CT images and histology was successful. GBPC-CT showed an improved soft tissue contrast compared to absorption-based images revealing more histological details in the same sections. Non-calcifying DCIS exceeding the invasive tumor could be correlated to areas of dilated bright ducts around the tumor. CONCLUSIONS: GBPC-CT imaging at conventional X-ray sources offers improved depiction quality for the imaging of breast tissue samples compared to absorption-based imaging, allows the identification of diagnostically relevant tissue details, and provides full three-dimensional assessment of sample margins.

Characteristics and associated risk factors of diverticular disease assessed by magnetic resonance imaging in subjects from a Western general population.

OBJECTIVES: Diverticular disease represents an increasing pathology and healthcare burden worldwide. Our aim was to study the prevalence, extent and distribution of asymptomatic diverticular disease assessed by magnetic resonance imaging (MRI) in a sample of a Western population. METHODS: Subjects from a population-based cohort study who underwent 3-T MRI were analyzed for the prevalence and extent of diverticula of the colon using an isotropic VIBE-Dixon gradient-echo sequence. The extent of diverticular disease was categorized according to the number of diverticula in each colonic segment. Univariate and adjusted analyses were performed to assess associated characteristics and risk factors. RESULTS: Among 393 subjects included in the analysis (56.4 ± 9.2 years, 57.5% males), 164 (42%) had diverticular disease, with the highest prevalence in the left-sided colonic segments (93% diverticular disease in the descending and sigmoid segment). Subjects with advanced diverticular disease were older (62.1 vs. 54.4 years) and had a higher body mass index (BMI), LDL cholesterol levels and systolic blood pressure (30.2 ± 5.1 vs. 27.8 ± 4.9 kg/m2, 149.8 ± 29.3 vs. 135.2 ± 32.9 mg/dl and 128.2 ± 14.1 vs. 118.4 ± 16.1 mmHg, respectively; all p > 0.003) compared with subjects without diverticular disease. In contrast, no significant correlation could be found for gender, physical activity, smoking status and alcohol consumption (all p > 0.31). Intra-rater reliability was excellent for all colonic segments (intra-class correlation [ICC] = 0.99-1.00), and inter-rater reliability was excellent for left- and right-sided colonic segments (ICC = 0.84-0.97). CONCLUSIONS: These findings provide insights into the disease mechanism of asymptomatic diverticular disease and may help to improve prevention of diverticulosis and its associated complications. KEY POINTS: • Overall prevalence of asymptomatic diverticular disease assessed by MRI was 42%, affecting predominantly the left-sided colon. • Asymptomatic diverticular disease was associated with age and cardiometabolic risk factors. • Magnetic resonance imaging reveals insights into the pathophysiologic mechanism of asymptomatic diverticular disease.

Integrin-targeted quantitative optoacoustic imaging with MRI correlation for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma.

PURPOSE: To investigate αvß3-integrin-targeted optoacoustic imaging and MRI for monitoring a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma. MATERIALS AND METHODS: Human BRAF V600E-positive melanoma xenograft (A375)-bearing Balb/c nude mice (n = 10) were imaged before (day 0) and after (day 7) a BRAF/MEK inhibitor combination therapy (encorafenib, 1.3 mg/kg/d; binimetinib, 0.6 mg/kg/d, n = 5) or placebo (n = 5), respectively. Optoacoustic imaging was performed on a preclinical system unenhanced and 5 h after i. v. injection of an αvß3-integrin-targeted fluorescent probe. The αvß3-integrin-specific tumor signal was derived by spectral unmixing. For morphology-based tumor response assessments, T2w MRI data sets were acquired on a clinical 3 Tesla scanner. The imaging results were validated by multiparametric immunohistochemistry (ß3 -integrin expression, CD31 -microvascular density, Ki-67 -proliferation). RESULTS: The αvß3-integrin-specific tumor signal was significantly reduced under therapy, showing a unidirectional decline in all animals (from 7.98±2.22 to 1.67±1.30; p = 0.043). No significant signal change was observed in the control group (from 6.60±6.51 to 3.67±1.93; p = 0.500). Immunohistochemistry revealed a significantly lower integrin expression (ß3: 0.20±0.02 vs. 0.39±0.05; p = 0.008) and microvascular density (CD31: 119±15 vs. 292±49; p = 0.008) in the therapy group. Tumor volumes increased with no significant intergroup difference (therapy: +107±42 mm3; control +112±44mm3, p = 0.841). In vivo blocking studies with αvß3-integrin antagonist cilengitide confirmed the target specificity of the fluorescent probe. CONCLUSIONS: αvß3-integrin-targeted optoacoustic imaging allowed for the early non-invasive monitoring of a BRAF/MEK inhibitor combination therapy in a murine model of human melanoma, adding molecular information on tumor receptor status to morphology-based tumor response criteria.

Dose-compatible grating-based phase-contrast mammography on mastectomy specimens using a compact synchrotron source.

With the introduction of screening mammography, the mortality rate of breast cancer has been reduced throughout the last decades. However, many women undergo unnecessary subsequent examinations due to inconclusive diagnoses from mammography. Two pathways appear especially promising to reduce the number of false-positive diagnoses. In a clinical study, mammography using synchrotron radiation was able to clarify the diagnosis in the majority of inconclusive cases. The second highly valued approach focuses on the application of phase-sensitive techniques such as grating-based phase-contrast and dark-field imaging. Feasibility studies have demonstrated a promising enhancement of diagnostic content, but suffer from dose concerns. Here we present dose-compatible grating-based phase-contrast and dark-field images as well as conventional absorption images acquired with monochromatic x-rays from a compact synchrotron source based on inverse Compton scattering. Images of freshly dissected mastectomy specimens show improved diagnostic content over ex-vivo clinical mammography images at lower or equal dose. We demonstrate increased contrast-to-noise ratio for monochromatic over clinical images for a well-defined phantom. Compact synchrotron sources could potentially serve as a clinical second level examination.

Global Challenges for Cancer Imaging.

Imaging plays many essential roles in nearly all aspects of high-quality cancer care. However, challenges to the delivery of optimal cancer imaging in both developing and advanced countries are manifold. Developing countries typically face dramatic shortages of both imaging equipment and general radiologists, and efforts to improve cancer imaging in these countries are often complicated by poor infrastructure, cultural barriers, and other obstacles. In advanced countries, on the other hand, although imaging equipment and general radiologists are typically accessible, the complexity of oncologic imaging and the need for subspecialists in the field are largely unrecognized; as a result, training opportunities are lacking, and there is a shortage of radiologists with the necessary subspecialty expertise to provide optimal cancer care and participate in advanced clinical research. This article is intended to raise awareness of these challenges and catalyze further efforts to address them. Some promising strategies and ongoing efforts are reviewed, and some specific actions are proposed.

Micro-imaging of Brain Cancer Radiation Therapy Using Phase-contrast Computed Tomography.

PURPOSE: Experimental neuroimaging provides a wide range of methods for the visualization of brain anatomic morphology down to subcellular detail. Still, each technique-specific detection mechanism presents compromises among the achievable field-of-view size, spatial resolution, and nervous tissue sensitivity, leading to partial sample coverage, unresolved morphologic structures, or sparse labeling of neuronal populations and often also to obligatory sample dissection or other sample invasive manipulations. X-ray phase-contrast imaging computed tomography (PCI-CT) is an experimental imaging method that simultaneously provides micrometric spatial resolution, high soft-tissue sensitivity, and ex vivo full organ rodent brain coverage without any need for sample dissection, staining or labeling, or contrast agent injection. In the present study, we explored the benefits and limitations of PCI-CT use for in vitro imaging of normal and cancerous brain neuromorphology after in vivo treatment with synchrotron-generated x-ray microbeam radiation therapy (MRT), a spatially fractionated experimental high-dose radiosurgery. The goals were visualization of the MRT effects on nervous tissue and a qualitative comparison of the results to the histologic and high-field magnetic resonance imaging findings. METHODS AND MATERIALS: MRT was administered in vivo to the brain of both healthy and cancer-bearing rats. At 45 days after treatment, the brain was dissected out and imaged ex vivo using propagation-based PCI-CT. RESULTS: PCI-CT visualizes the brain anatomy and microvasculature in 3 dimensions and distinguishes cancerous tissue morphology, necrosis, and intratumor accumulation of iron and calcium deposits. Moreover, PCI-CT detects the effects of MRT throughout the treatment target areas (eg, the formation of micrometer-thick radiation-induced tissue ablation). The observed neurostructures were confirmed by histologic and immunohistochemistry examination and related to the micro-magnetic resonance imaging data. CONCLUSIONS: PCI-CT enabled a unique 3D neuroimaging approach for ex vivo studies on small animal models in that it concurrently delivers high-resolution insight of local brain tissue morphology in both normal and cancerous micro-milieu, localizes radiosurgical damage, and highlights the deep microvasculature. This method could assist experimental small animal neurology studies in the postmortem evaluation of neuropathology or treatment effects.

CT attenuation of liver metastases before targeted therapy is a prognostic factor of overall survival in colorectal cancer patients. Results from the randomised, open-label FIRE-3/AIO KRK0306 trial.

OBJECTIVES: To assess the prognostic value of pre-therapeutic computed tomography (CT) attenuation of liver metastases for overall survival (OS) in metastatic colorectal cancer (mCRC). METHODS: In the open-label, randomised, prospective phase-III FIRE-3 trial, patients with histologically confirmed mCRC received fluorouracil (5-FU), leucovorin and irinotecan (FOLFIRI) with either cetuximab or bevacizumab. Participating patients gave written informed consent prior to study entry. In CT at baseline (portal venous phase, slice thickness ≤5 mm), mean attenuation [Hounsfield units (HU)] of liver metastases was retrospectively assessed by semi-automated volumetry. Its prognostic influence on OS was analysed in Kaplan-Meier-analysis and Cox proportional hazard regression and an optimal threshold was determined. RESULTS: In FIRE-3, 592 patients were enrolled between 2007 and 2012. Among the 347 patients eligible for liver volumetry, median baseline CT attenuation of liver metastases was 59.67 HU [interquartile range (IQR), 49.13, 68.85]. Increased attenuation was associated with longer OS {per 10 HU: hazard ratio (HR), 0.85 [95% confidence interval (CI), 0.78, 0.93], p < 0.001}. The optimised threshold (≥61.62 HU) was a strong predictor for increased OS [median, 21.3 vs 30.6 months; HR, 0.61 (95% CI, 0.47, 0.80), p < 0.001]. Multivariate regression controlling for correlated and further prognostic factors confirmed this [HR, 0.60 (95% CI, 0.45, 0.81), p = 0.001]. Furthermore, mean attenuation ≥61.62 HU was significantly associated with increased early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012). CONCLUSIONS: Increased mean baseline CT attenuation of liver metastases may identify mCRC patients with prolonged OS and better tumour response. KEY POINTS: • In colorectal cancer, increased attenuation of liver metastases in baseline computed tomography is a prognostic factor for prolonged OS (p < 0.001). • A threshold of ≥61.62 HU was determined as optimal cut-off to identify patients with prolonged OS (p < 0.001), early tumour shrinkage (p = 0.002) and increased depth of response (p = 0.012).

CT fluoroscopy-guided percutaneous osteoplasty with or without radiofrequency ablation in the treatment of painful extraspinal and spinal bone metastases: technical outcome and complications in 29 patients.

PURPOSE: We aimed to assess the safety and technical outcome of computed tomography (CT) fluoroscopy-guided osteoplasty with or without prior percutaneous radiofrequency ablation (RFA) in patients with painful osteolyses. METHODS: We performed a retrospective analysis of 29 patients with painful extraspinal and spinal osteolyses (16 women, 13 men; 63.1±14.4 years) who underwent CT fluoroscopy-guided osteoplasty (10-20 mAs tube current) with or without RFA (26 and 14 lesions, respectively), in 33 consecutive procedures from 2002 to 2016. Technical success was defined as at least one complete RFA cycle and subsequent polymethyl metacrylate (PMMA) bone cement injection covering ≥75% of longest diameter of extraspinal osteolysis on axial plane or of distance between vertebral endplates. Procedure-related complications within 30 days and dose-length-product (DLP) were also evaluated. RESULTS: Osteolyses were located in the pelvis (acetabulum, n=10; iliac bone, n=4), spine (thoracic, n=6; lumbar, n=5; sacral, n=8), long bones (femur, n=3; tibia, n=1), sternum (n=2) and glenoid (n=1). Mean size of the treated osteolysis was 4.0±1.2 cm (range, 1.9-6.9 cm). Of 40 osteolyses, 31 (77.5%) abutted neighboring risk structures (spinal canal or neuroforamen, n=18; neighboring joint, n=11; other, n=8). Mean number of RFA electrode positions and complete ablation cycles was 1.5±0.9 and 2.1±1.7, respectively. Mean PMMA filling volume was 7.7±5.7 mL (range, 2-30 mL). Small asymptomatic PMMA leakages were observed in 15 lesions (37.5%). Mean total DLP was 850±653 mGy*cm. Six minor complications were observed, without any major complications. CONCLUSION: CT fluoroscopy-guided percutaneous osteoplasty with or without concomitant RFA for the treatment of painful extraspinal and spinal osteolyses can be performed with a low complication rate and high technical success.

Quantitative Assessment of Degenerative Cartilage and Subchondral Bony Lesions in a Preserved Cadaveric Knee: Propagation-Based Phase-Contrast CT Versus Conventional MRI and CT.

OBJECTIVE: The aim of this study was to quantitatively assess hyaline cartilage and subchondral bone conditions in a fully preserved cadaveric human knee joint using high-resolution x-ray propagation-based phase-contrast imaging (PBI) CT and to compare the performance of the new technique with conventional CT and MRI. MATERIALS AND METHODS: A cadaveric human knee was examined using an x-ray beam of 60 keV, a detector with a 90-mm2 FOV, and a pixel size of 46 × 46 µm2. PBI CT images were reconstructed with both the filtered back projection algorithm and the equally sloped tomography method. Conventional 3-T MRI and CT were also performed. Measurements of cartilage thickness, cartilage lesions, International Cartilage Repair Society scoring, and detection of subchondral bone changes were evaluated. Visual inspection of the specimen akin to arthroscopy was conducted and served as a standard of reference for lesion detection. RESULTS: Loss of cartilage height was visible on PBI CT and MRI. Quantification of cartilage thickness showed a strong correlation between the two modalities. Cartilage lesions appeared darker than the adjacent cartilage on PBI CT. PBI CT showed similar agreement to MRI for depicting cartilage substance defects or lesions compared with the visual inspection. The assessment of subchondral bone cysts showed moderate to strong agreement between PBI CT and CT. CONCLUSION: In contrast to the standard clinical methods of MRI and CT, PBI CT is able to simultaneously depict cartilage and bony changes at high resolution. Though still an experimental technique, PBI CT is a promising high-resolution imaging method to evaluate comprehensive changes of osteoarthritic disease in a clinical setting.