CT-Guided Liver Biopsy: Evaluation of Spectral Data From Dual-Layer Detector CT for Improved Lesion Detection.

PURPOSE: Evaluation of dual-layer spectral computed tomography (CT) for contrast enhancement during image-guided biopsy of liver lesions using virtual monoenergetic images (VMI) and virtual non-contrast (VNC) images. METHODS: Spectral CT data of 20 patients receiving CT-guided needle biopsy of focal liver lesions were used to generate VMI at energy levels from 40 to 200 keV and VNC images. Images were analyzed objectively regarding contrast-to-noise ratio between lesion center (CNRcent) or periphery (CNRperi) and normal liver parenchyma. Lesion visibility and image quality were evaluated on a 4-point Likert scale by two radiologists. RESULTS: Using VMI/VNC images, readers reported an increased visibility of the lesion compared to the conventional CT images in 18/20 cases. In 75% of cases, the highest visibility was derived by VMI-40. Showing all reconstructions simultaneously, VMI-40 offered the highest visibility in 75% of cases, followed by VNC in 12.5% of cases. Either CNRcent (17/20) or/and CNRperi (17/20) was higher (CNR increase > 50%) in 19/20 cases for VMI-40 or VNC images compared to conventional CT images. VMI-40 showed the highest CNRcent in 14 cases and the highest CNRperi in 12 cases. High image quality was present for all reconstructions with a minimum median of 3.5 for VMI-40 and VMI-50. CONCLUSIONS: When implemented in the CT scanner software, automated contrast enhancement of liver lesions during image-guided biopsy may facilitate the procedure.

X-ray Dark-Field CT for Early Detection of Radiation-induced Lung Injury in a Murine Model.

Online supplemental material is available for this article.

In-vivo X-ray dark-field computed tomography for the detection of radiation-induced lung damage in mice.

BACKGROUND AND PURPOSE: Radiotherapy of thoracic tumours can lead to side effects in the lung, which may benefit from early diagnosis. We investigated the potential of X-ray dark-field computed tomography by a proof-of-principle murine study in a clinically relevant radiotherapeutic setting aiming at the detection of radiation-induced lung damage. MATERIAL AND METHODS: Six mice were irradiated with 20 Gy to the entire right lung. Together with five unirradiated control mice, they were imaged using computed tomography with absorption and dark-field contrast before and 16 weeks post irradiation. Mean pixel values for the right and left lung were calculated for both contrasts, and the right-to-left-ratio R of these means was compared. Radiologists also assessed the tomograms acquired 16 weeks post irradiation. Sensitivity, specificity, inter- and intra-reader accuracy were evaluated. RESULTS: In absorption contrast the group-average of R showed no increase in the control group and increased by 7% (p = 0.005) in the irradiated group. In dark-field contrast, it increased by 2% in the control group and by 14% (p = 0.005) in the irradiated group. Specificity was 100% for both contrasts but sensitivity was almost four times higher using dark-field tomography. Two cases were missed by absorption tomography but were detected by dark-field tomography. CONCLUSIONS: The applicability of X-ray dark-field computed tomography for the detection of radiation-induced lung damage was demonstrated in a pre-clinical mouse model. The presented results illustrate the differences between dark-field and absorption contrast and show that dark-field tomography could be advantageous in future clinical settings.

X-ray dark-field chest imaging for detection and quantification of emphysema in patients with chronic obstructive pulmonary disease: a diagnostic accuracy study.

BACKGROUND: Although advanced medical imaging technologies give detailed diagnostic information, a low-dose, fast, and inexpensive option for early detection of respiratory diseases and follow-ups is still lacking. The novel method of x-ray dark-field chest imaging might fill this gap but has not yet been studied in living humans. Enabling the assessment of microstructural changes in lung parenchyma, this technique presents a more sensitive alternative to conventional chest x-rays, and yet requires only a fraction of the dose applied in CT. We studied the application of this technique to assess pulmonary emphysema in patients with chronic obstructive pulmonary disease (COPD). METHODS: In this diagnostic accuracy study, we designed and built a novel dark-field chest x-ray system (Technical University of Munich, Munich, Germany)-which is also capable of simultaneously acquiring a conventional thorax radiograph (7 s, 0·035 mSv effective dose). Patients who had undergone a medically indicated chest CT were recruited from the department of Radiology and Pneumology of our site (Klinikum rechts der Isar, Technical University of Munich, Munich, Germany). Patients with pulmonary pathologies, or conditions other than COPD, that might influence lung parenchyma were excluded. For patients with different disease stages of pulmonary emphysema, x-ray dark-field images and CT images were acquired and visually assessed by five readers. Pulmonary function tests (spirometry and body plethysmography) were performed for every patient and for a subgroup of patients the measurement of diffusion capacity was performed. Individual patient datasets were statistically evaluated using correlation testing, rank-based analysis of variance, and pair-wise post-hoc comparison. FINDINGS: Between October, 2018 and December, 2019 we enrolled 77 patients. Compared with CT-based parameters (quantitative emphysema ρ=-0·27, p=0·089 and visual emphysema ρ=-0·45, p=0·0028), the dark-field signal (ρ=0·62, p<0·0001) yields a stronger correlation with lung diffusion capacity in the evaluated cohort. Emphysema assessment based on dark-field chest x-ray features yields consistent conclusions with findings from visual CT image interpretation and shows improved diagnostic performance than conventional clinical tests characterising emphysema. Pair-wise comparison of corresponding test parameters between adjacent visual emphysema severity groups (CT-based, reference standard) showed higher effect sizes. The mean effect size over the group comparisons (absent-trace, trace-mild, mild-moderate, and moderate-confluent or advanced destructive visual emphysema grades) for the COPD assessment test score is 0·21, for forced expiratory volume in 1 s (FEV1)/functional vital capacity is 0·25, for FEV1% of predicted is 0·23, for residual volume % of predicted is 0·24, for CT emphysema index is 0·35, for dark-field signal homogeneity within lungs is 0·38, for dark-field signal texture within lungs is 0·38, and for dark-field-based emphysema severity is 0·42. INTERPRETATION: X-ray dark-field chest imaging allows the diagnosis of pulmonary emphysema in patients with COPD because this technique provides relevant information representing the structural condition of lung parenchyma. This technique might offer a low radiation dose alternative to CT in COPD and potentially other lung disorders. FUNDING: European Research Council, Deutsche Forschungsgemeinschaft, Royal Philips, and Karlsruhe Nano Micro Facility.

Improved differentiation between primary lung cancer and pulmonary metastasis by combining dual-energy CT-derived biomarkers with conventional CT attenuation.

OBJECTIVES: To assess the clinical utility of dual-energy CT (DE-CT)-derived iodine concentration (IC) and effective Z (Zeff) in addition to conventional CT attenuation (HU) for the discrimination between primary lung cancer (LC) and pulmonary metastases (PM) from different primary malignancies. METHODS: DE-CT scans of 79 patients with LC (3 histopathologic subgroups) and 89 patients with PM (5 histopathologic subgroups) were evaluated. Quantitative IC, Zeff, and conventional HU values were extracted and normalized to the thoracic aorta. Differences between groups were assessed by pairwise Welch's t test. Correlation and linear regression analyses were used to examine the relationship of imaging parameters in LC and PM. Diagnostic accuracy was measured by the area under receiver operator characteristic curve (AUC) and validated based on resampling methods. RESULTS: Significant differences between subgroups of LC and PMs were noted for all imaging parameters, with the highest number of significant pairs for IC. In univariate analysis, only IC was a significant diagnostic feature for discriminating LC from PM (p = 0.03). All quantitative imaging parameters correlated significantly (p < 0.0001, respectively), with the highest correlation between IC and Zeff (r = 0.91), followed by IC and HU (r = 0.76) and Zeff and HU (r = 0.73). Diagnostic models combining IC or Zeff with HU (IC+HU: AUC = 0.73; Zeff+HU: AUC = 0.69; IC+Zeff+HU: AUC = 0.73) were not significantly different and outperformed individual parameters (IC: AUC = 0.57; Zeff: AUC = 0.57; HU: AUC = 0.55) in diagnostic accuracy (p < 0.05, respectively). CONCLUSION: DE-CT-derived IC or Zeff and conventional HU represent complementary imaging parameters, which, if used in combination, may improve the differentiation between LC and PM. KEY POINTS: • Individual quantitative imaging parameters derived from DE-CT (iodine concentration, effective Z) and conventional CT (HU) provide complementary diagnostic information for the differentiation of primary lung cancer and pulmonary metastases. • A combination of conventional HU and DE-CT parameters enhances the diagnostic utility of individual parameters.

Dual-energy CT parameters in correlation to MRI-based apparent diffusion coefficient: evaluation in rectal cancer after radiochemotherapy.

BACKGROUND: Rectal cancer (RC) is a frequent malignancy for which magnetic resonance imaging (MRI) is the most common and accurate imaging. Iodine concentration (IC) can be quantified with spectral dual-layer computed tomography CT (DL-CT), which could improve imaging of RC, especially for evaluation of response to radiochemotherapy (RCT). PURPOSE: To compare a DL-CT system to MRI as the non-invasive imaging gold standard for imaging of RC to evaluate the possibility of a response evaluation with DL-CT. MATERIAL AND METHODS: Eleven patients who received DL-CT as well as MRI before and after RCT of RC were retrospectively included into this study. For each examination, a region of interest (ROI) was placed within the tumor. For MRI, the mean apparent diffusion coefficient (ADC) was assessed. For DL-CT, IC, z-effective, and Hounsfield Units (HU) were measured. IC, z-effective, and HU were normalized to the aorta. ADC was correlated to absolute and relative normalized IC, z-effective, and HU with Spearman's ρ. Differences before and after treatment were tested with Wilcoxon signed-rank test. RESULTS: HU, IC, and Z-effective values in DL-CT images decreased significantly after RCT (P<0.01 for each comparison). The mean ADC increased significantly after RCT. Spearman's ρ of the absolute IC difference and the absolute ADC (both before and after RCT) is high and significant (ρ = 0.73; P = 0.01), whereas the ρ-value for z-effective (ρ = 0.56) or HU (ρ = 0.45) to ADC was lower and non-significant. CONCLUSION: Response evaluation of RC after RCT could be possible with DL-CT via the measurement of IC.

Diffusion tensor imaging and tractography for preoperative assessment of benign peripheral nerve sheath tumors.

PURPOSE: To evaluate the diagnostic value of fiber tractography and diffusivity analysis generated from 3D diffusion-weighted (DW) sequences for preoperative assessment of benign peripheral nerve sheath tumors. METHOD: MR imaging at 3 T was performed in 22 patients (mean age 41.9 ±â€¯17.1y, 13 women) with histologically confirmed schwannomas (N = 18) and histologically confirmed neurofibromas (N = 11), including a 3D DW turbo spin echo sequence with fat suppression. Diffusion tensor parameters were computed and fiber tracks were determined. Evaluation was performed by two radiologists and one orthopedic surgeon blinded for final diagnosis. Mean diffusivity was computed to allow further assessment of tumor microstructure. Preoperative fascicle visualization was graded, fascicles were categorized regarding anatomical location and amount of fascicles surrounding the tumor. The agreement of imaging findings with intraoperative findings was assessed. RESULTS: On 78.3 % of the DTI images, the fascicle visualization was rated as good or very good. Tractography differences were observed in schwannomas and neurofibromas, showing schwannomas to be significantly more often located eccentrically to the nerve (94.8 %) than neurofibromas (0 %, P < 0.01). Fascicles were significantly more often continuous (87.5 %) in schwannomas, while in neurofibromas, none of the tracks was graded to be continuous (0 %, P = 0.014). A substantial agreement between fiber tracking and surgical anatomy was found regarding the fascicle courses surrounding the tumor (κ = 0.78). Mean diffusivity of schwannomas (1.5 ±â€¯0.2 × 10-3 mm2/s) was significantly lower than in neurofibromas (1.8 ±â€¯0.2 × 10-3 mm2/s; P < 0.001). The Youden index showed an optimal cutoff at 1.7 × 10-3 mm2/s (sensitivity, 0.91; specificity, 0.78; J = 0.69). CONCLUSIONS: Preoperative diffusion tensor imaging allowed to accurately differentiate between schwannomas and neurofibromas and to describe their location in relation to the nerve fascicles for preoperative planning.

Age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content.

This analysis investigated the age- and BMI-related variations of fat distribution in sacral and lumbar bone marrow and their association with local muscle fat content in order to detect fat distribution patterns and variations in healthy adults using proton density fat fraction (PDFF) measurements. A six-echo 3D spoiled gradient-echo sequence was used for chemical shift encoding-based water-fat separation at the sacral and lower lumbar region in 103 healthy volunteers. PDFF values of the sacrum, 5th lumbar vertebral body, the gluteal and paraspinal muscles were determined. Correlation with age was significant (p < 0.05) for PDFF of the sacrum (men (m): r = 0.58; women (w): r = 0.54), L5 (m: r = 0.58; w: r = 0.54), the gluteal (m: r = 0.51; w: r = 0.44) and paraspinal (m: r = 0.36; w: r = 0.49) muscles in both genders. BMI correlated significantly with the paraspinal musculature in men (r = 0.46) and women (r = 0.33). Correlation testing revealed significant correlations (p < 0.05) between the two osseous (m: r = 0.63, w: r = 0.75) and the muscle compartments (m: r = 0.63, w: r = 0.33) in both genders. Bone marrow and muscle fat infiltration patterns were not significantly associated with each other at the sacral and lower lumbar spine region. The presented data suggest that the two compartments may have distinct pathophysiological fat infiltration patterns. However, further clinical studies are needed to support the results.

CTPA with a conventional CT at 100 kVp vs. a spectral-detector CT at 120 kVp: Comparison of radiation exposure, diagnostic performance and image quality.

PURPOSE: To compare CT pulmonary angiographies (CTPAs) as well as phantom scans obtained at 100 kVp with a conventional CT (C-CT) to virtual monochromatic images (VMI) obtained with a spectral detector CT (SD-CT) at equivalent dose levels as well as to compare the radiation exposure of both systems. MATERIAL AND METHODS: In total, 2110 patients with suspected pulmonary embolism (PE) were examined with both systems. For each system (C-CT and SD-CT), imaging data of 30 patients with the same mean CT dose index (4.85 mGy) was used for the reader study. C-CT was performed with 100 kVp and SD-CT was performed with 120 kVp; for SD-CT, virtual monochromatic images (VMI) with 40, 60 and 70 keV were calculated. All datasets were evaluated by three blinded radiologists regarding image quality, diagnostic confidence and diagnostic performance (sensitivity, specificity). Contrast-to-noise ratio (CNR) for different iodine concentrations was evaluated in a phantom study. RESULTS: CNR was significantly higher with VMI at 40 keV compared to all other datasets. Subjective image quality as well as sensitivity and specificity showed the highest values with VMI at 60 keV and 70 keV. Hereby, a significant difference to 100 kVp (C-CT) was found for image quality. The highest sensitivity was found using VMI at 60 keV with a sensitivity of more than 97 % for all localizations of PE. For diagnostic confidence and subjective contrast, highest values were found with VMI at 40 keV. CONCLUSION: Higher levels of diagnostic performance and image quality were achieved for CPTAs with SD-CT compared to C-CT given similar dose levels. In the clinical setting SD-CT may be the modality of choice as additional spectral information can be obtained.

Gold Nanoparticle Mediated Multi-Modal CT Imaging of Hsp70 Membrane-Positive Tumors.

Imaging techniques such as computed tomographies (CT) play a major role in clinical imaging and diagnosis of malignant lesions. In recent years, metal nanoparticle platforms enabled effective payload delivery for several imaging techniques. Due to the possibility of surface modification, metal nanoparticles are predestined to facilitate molecular tumor targeting. In this work, we demonstrate the feasibility of anti-plasma membrane Heat shock protein 70 (Hsp70) antibody functionalized gold nanoparticles (cmHsp70.1-AuNPs) for tumor-specific multimodal imaging. Membrane-associated Hsp70 is exclusively presented on the plasma membrane of malignant cells of multiple tumor entities but not on corresponding normal cells, predestining this target for a tumor-selective in vivo imaging. In vitro microscopic analysis revealed the presence of cmHsp70.1-AuNPs in the cytosol of tumor cell lines after internalization via the endo-lysosomal pathway. In preclinical models, the biodistribution as well as the intratumoral enrichment of AuNPs were examined 24 h after i.v. injection in tumor-bearing mice. In parallel to spectral CT analysis, histological analysis confirmed the presence of AuNPs within tumor cells. In contrast to control AuNPs, a significant enrichment of cmHsp70.1-AuNPs has been detected selectively inside tumor cells in different tumor mouse models. Furthermore, a machine-learning approach was developed to analyze AuNP accumulations in tumor tissues and organs. In summary, utilizing mHsp70 on tumor cells as a target for the guidance of cmHsp70.1-AuNPs facilitates an enrichment and uniform distribution of nanoparticles in mHsp70-expressing tumor cells that enables various microscopic imaging techniques and spectral-CT-based tumor delineation in vivo.

Regional variation in paraspinal muscle composition using chemical shift encoding-based water-fat MRI.

BACKGROUND: Paraspinal musculature forms one of the largest muscle compartments of the human body, but evidence for regional variation of its composition and dependency on gender or body mass index (BMI) is scarce. METHODS: This study applied six-echo chemical shift encoding-based water-fat magnetic resonance imaging (MRI) at 3 Tesla in 76 subjects (24 males and 52 females, age: 40.0±13.7 years, BMI: 25.4±5.6 kg/m2) to evaluate the proton density fat fraction (PDFF) of psoas muscles and erector spinae muscles, with the latter being divided into three segments in relation to levels of spine anatomy (L3-L5, T12-L2, and T9-T11). RESULTS: For the psoas muscles and the erector spinae muscles (L3-L5), gender differences in PDFF values were observed (PDFF psoas muscles: males: 5.1%±3.4% vs. females: 6.0%±2.2%, P=0.006; PDFF erector spinae muscles L3-L5: males: 10.7%±7.6% vs. females: 18.2%±6.8%, P<0.001). Furthermore, the PDFF of the erector spinae muscles (L3-L5) showed higher PDFF values when compared to the other segments (PDFF erector spinae muscles L3-L5 vs. T12-L2: P<0.001; PDFF erector spinae muscles L3-L5 vs. T9-T11: P<0.001) and showed to be independent of BMI, which was not the case for the other segments (T12-L2 or T9-T11) or the psoas muscles. When considering age and BMI as control variables, correlations of PDFF between segments of the erector spinae muscles remained significant for both genders. CONCLUSIONS: This study explored regional variation of paraspinal muscle composition and dependency on gender and BMI, thus offering new insights into muscle physiology. The PDFF of the erector spinae muscles (L3-L5) was independent of BMI, suggesting that this level may be suited for representative paraspinal muscle segmentation and PDFF extraction as a biomarker for muscle alterations in the future.

Longitudinal imaging of T cell-based immunotherapy with multi-spectral, multi-scale optoacoustic tomography.

Most imaging studies of immunotherapy have focused on tracking labeled T cell biodistribution in vivo for understanding trafficking and homing parameters and predicting therapeutic efficacy by the presence of transferred T cells at or in the tumour mass. Conversely, we investigate here a novel concept for longitudinally elucidating anatomical and pathophysiological changes of solid tumours after adoptive T cell transfer in a preclinical set up, using previously unexplored in-tandem macroscopic and mesoscopic optoacoustic (photoacoustic) imaging. We show non-invasive in vivo observations of vessel collapse during tumour rejection across entire tumours and observe for the first time longitudinal tumour rejection in a label-free manner based on optical absorption changes in the tumour mass due to cellular decline. We complement these observations with high resolution episcopic fluorescence imaging of T cell biodistribution using optimized T cell labeling based on two near-infrared dyes targeting the cell membrane and the cytoplasm. We discuss how optoacoustic macroscopy and mesoscopy offer unique contrast and immunotherapy insights, allowing label-free and longitudinal observations of tumour therapy. The results demonstrate optoacoustic imaging as an invaluable tool in understanding and optimizing T cell therapy.

Iodine concentration of healthy lymph nodes of neck, axilla, and groin in dual-energy computed tomography.

BACKGROUND: Lymph nodes (LN) are examined in every computed tomography (CT) scan. Until now, an evaluation is only possible based on morphological criteria. With dual-energy CT (DECT) systems, iodine concentration (IC) can be measured which could conduct in an improved diagnostic evaluation of LNs. PURPOSE: To define standard values for IC of cervical, axillary, and inguinal LNs in DECT. MATERIAL AND METHODS: Imaging data of 297 patients who received a DECT scan of the neck, thorax, abdomen-pelvis, or a combination of those in a portal-venous phase were retrospectively collected from the institutional PACS. No present history of malignancy, inflammation, or trauma in the examined region was present. For each examined region, the data of 99 patients were used. The IC of the three largest LNs, the main artery, the main vein, and a local muscle of the examined area was measured, respectively. RESULTS: Normalization of the IC of LNs to the artery, vein, muscle, or a combination of those did not lead to a decreased value-range. The smallest range and confidence interval (CI) of IC was found when using absolute values of IC for each region. Hereby, mean values (95% CI) for IC of LN were found: 2.09 mg/mL (2.00-2.18 mg/mL) for neck, 1.24 mg/mL (1.16-1.33 mg/mL) for axilla, and 1.11 mg/mL (1.04-1.17 mg/mL) for groin. CONCLUSION: The present study suggests standard values for IC of LNs in dual-layer CT could be used to differentiate between healthy and pathological lymph nodes, considering the used contrast injection protocol.

Combined DCE-MRI- and FDG-PET enable histopathological grading prediction in a rat model of hepatocellular carcinoma.

PURPOSE: To test combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-FDG positron emission tomography (FDG-PET)-derived parameters for prediction of histopathological grading in a rat Diethyl Nitrosamine (DEN)-induced hepatocellular carcinoma (HCC) model. METHODS: 15 male Wistar rats, aged 10 weeks were treated with oral DEN 0.01 % in drinking water and monitored until HCCs were detectable. DCE-MRI and PET were performed consecutively on small animal scanners. 38 tumors were identified and manually segmented based on HCC-specific contrast enhancement patterns. Grading (G2/3: 24 tumors, G1:14 tumors) alongside other histopathological parameters, tumor volume, contrast agent and 18F-FDG uptake metrics were noted. Class imbalance was addressed using SMOTE and collinearity was removed using hierarchical clustering and principal component analysis. A logistic regression model was fit separately to the individual parameter groups (DCE-MRI-derived, PET-derived, tumor volume) and the combined parameters. RESULTS: The combined model using all imaging-derived parameters achieved a mean ± STD sensitivity of 0.88 ± 0.16, specificity of 0.70 ± 0.20 and AUC of 0.90 ± 0.03. No correlation was found between tumor grading and tumor volume, morphology, necrosis, extracellular matrix, immune cell infiltration or underlying liver fibrosis. CONCLUSION: A combination of DCE-MRI- and 18F-FDG-PET-derived parameters provides high accuracy for histopathological grading of hepatocellular carcinoma in a relevant translational model system.

Association of thigh and paraspinal muscle composition in young adults using chemical shift encoding-based water-fat MRI.

BACKGROUND: Paraspinal and thigh muscles comprise the major muscle groups of the body. We investigated the composition of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups and their association to each other using chemical shift encoding-based water-fat magnetic resonance imaging (MRI) in adult volunteers. Our aim was to elucidate fat distribution patterns within these muscle groups. METHODS: Thirty volunteers [15 males, age: 30.5±4.9 years, body mass index (BMI): 27.6±2.8 kg/m2 and 15 females, age: 29.9±7.0 years, BMI: 25.8±1.4 kg/m2] were recruited for this study. A six-echo 3D spoiled gradient echo sequence was used for chemical shift encoding-based water-fat separation at the lumbar spine and bilateral thigh. Proton density fat fraction (PDFF), cross-sectional area (CSA) and contractile mass index (CMI) of the psoas, erector spinae, quadriceps femoris and hamstring muscle groups were determined bilaterally and averaged over both sides. RESULTS: CSA and CMI values calculated for the erector spinae, psoas, quadriceps and hamstring muscle groups showed significant differences between men and women (P<0.05). With regard to PDFF measurement only the erector spinae showed significant differences between men and women (9.5%±2.4% vs. 11.7%±2.8%, P=0.015). The CMI of the psoas muscle as well as the erector spinae muscle showed significant correlations with the quadriceps muscle (r=0.691, P<0.0001 and r=0.761, P<0.0001) and the hamstring group (r=0.588, P=0.001 and r=0.603, P<0.0001). CONCLUSIONS: CMI values of the erector spinae and psoas muscles were associated with those of the quadriceps femoris and hamstring musculature. These findings suggest a concordant spatial fat accumulation within the analyzed muscles in young adults and warrants further investigations in ageing and diseased muscle.

Grating-based phase-contrast CT (PCCT): histopathological correlation of human liver cirrhosis and hepatocellular carcinoma specimen.

AIMS: To correlate signal intensities in grating-based phase-contrast CT (PCCT) images obtained at a synchrotron light source and a conventional X-ray source with tissue components in human liver cirrhosis and hepatocellular carcinoma (HCC) specimen. METHODS: Study approval was obtained by the institutional review board. Human specimen of liver cirrhosis and HCC were imaged at experimental grating-based PCCT setups using either a synchrotron radiation source or a conventional X-ray tube. Tissue samples were sectioned and processed for H&E and Elastica van Gieson staining. PCCT and histological images were manually correlated. Depending on morphology and staining characteristics tissue components like fibrosis, HCC, inflammation, connective tissue and necrosis were differentiated and visually correlated with signal intensity in PCCT images using a 5-point Likert scale with normal liver parenchyma as a reference. RESULTS: Grating-based PCCT images of human cirrhotic liver and HCC specimen showed high soft-tissue contrast allowing correlation with histopathological sections. Signal intensities were similar in both setups independent of the nature of the radiation source. Connective tissue and areas of haemorrhage displayed the highest signal intensities, fibrotic liver tissue the lowest. CONCLUSIONS: Grating-based PCCT provides comparable results for the characterisation of human specimen of liver cirrhosis and HCC using either a synchrotron light source or a conventional X-ray tube. Due to its high soft-tissue contrast and its applicability to conventional X-ray tubes grating-based PCCT holds potential for preclinical research and virtual histology applications.

Bifunctional Labeling of Rabbit Mesenchymal Stem Cells for MR Imaging and Fluorescence Microscopy.

PURPOSE: Longitudinal imaging studies are important in the translational process of stem cell-based therapies. Small animal imaging models are widely available and practical but insufficiently depict important morphologic detail. In contrary, large animal models are logistically challenging and costly but offer greater imaging quality. In order to combine the advantages of both, we developed an intermediate-sized rabbit animal model for cartilage imaging studies. PROCEDURES: Rabbit mesenchymal stem cells (rMSC) were isolated as primary cultures from the bone marrow of New Zealand white rabbits. rMSC were subsequentially transduced lentivirally with eGFP and magnetically labeled with the iron oxide ferucarbotran. eGFP expression was evaluated by flow cytometry and iron uptake was analyzed by isotope dilution mass spectrometry and Prussian blue staining. Fluorescence microscopy of eGFP-transduced rMSC was performed. Viability and induction of apoptosis were assessed by XTT and caspase-3/-7 measurements. The chondrogenic potential of labeled cells was quantified by glycosaminoglycan contents in TGF-ß3 induced pellet cultures. Labeled and unlabeled cells underwent magnetic resonance imaging (MRI) at 1.5 T before and after differentiation using T1-, T2-, and T2*-weighted pulse sequences. Relaxation rates were calculated. rMSCs were implanted in fibrin clots in osteochondral defects of cadaveric rabbit knees and imaged by 7 T MRI. T2* maps were calculated. Statistical analyses were performed using multiple regression models. RESULTS: Efficiency of lentiviral transduction was greater than 90 %. Fluorescence signal was dose dependent. Cellular iron uptake was significant for all concentrations (p < 0.05) and dose dependent (3.3-56.5 pg Fe/cell). Labeled rMSC showed a strong, dose-dependent contrast on all MR pulse sequences and a significant decrease in T2 and T2* relaxation rates. Compared with non-transduced or unlabeled controls, there were no adverse effects on cell viability, rate of apoptosis, or chondrogenic differentiation. MRI of labeled rMSCs in osteochondral defects showed a significant signal of the transplant with additional high-resolution anatomical information. CONCLUSIONS: This intermediate-sized rabbit model and its bifunctional labeling technique allow for improved depiction of anatomic detail for noninvasive in vivo rMSC tracking with MRI and for immunohistological correlation by fluorescence microscopy.

Liver lesion localisation and classification with convolutional neural networks: a comparison between conventional and spectral computed tomography.

PURPOSE: To evaluate the benefit of the additional available information present in spectral CT datasets, as compared to conventional CT datasets, when utilizing convolutional neural networks for fully automatic localisation and classification of liver lesions in CT images. MATERIALS AND METHODS: Conventional and spectral CT images (iodine maps, virtual monochromatic images (VMI)) were obtained from a spectral dual-layer CT system. Patient diagnosis were known from the clinical reports and classified into healthy, cyst and hypodense metastasis. In order to compare the value of spectral versus conventional datasets when being passed as input to machine learning algorithms, we implemented a weakly-supervised convolutional neural network (CNN) that learns liver lesion localisation without pixel-level ground truth annotations. Regions-of-interest are selected automatically based on the localisation results and are used to train a second CNN for liver lesion classification (healthy, cyst, hypodense metastasis). The accuracy of lesion localisation was evaluated using the Euclidian distances between the ground truth centres of mass and the predicted centres of mass. Lesion classification was evaluated by precision, recall, accuracy and F1-Score. RESULTS: Lesion localisation showed the best results for spectral information with distances of 8.22 ± 10.72 mm, 8.78 ± 15.21 mm and 8.29 ± 12.97 mm for iodine maps, 40 keV and 70 keV VMIs, respectively. With conventional data distances of 10.58 ± 17.65 mm were measured. For lesion classification, the 40 keV VMIs achieved the highest overall accuracy of 0.899 compared to 0.854 for conventional data. CONCLUSION: An enhanced localisation and classification is reported for spectral CT data, which demonstrates that combining machine-learning technology with spectral CT information may in the future improve the clinical workflow as well as the diagnostic accuracy.

Vertebral bone marrow fat fraction changes in postmenopausal women with breast cancer receiving combined aromatase inhibitor and bisphosphonate therapy.

BACKGROUND: Quantification of vertebral bone marrow (VBM) water-fat composition has been proposed as advanced imaging biomarker for osteoporosis. Estrogen deficiency is the primary reason for trabecular bone loss in postmenopausal women. By reducing estrogen levels aromatase inhibitors (AI) as part of breast cancer therapy promote bone loss. Bisphosphonates (BP) are recommended to counteract this adverse drug effect. The purpose of our study was to quantify VBM proton density fat fraction (PDFF) changes at the lumbar spine using chemical shift encoding-based water-fat MRI (CSE-MRI) and bone mineral density (BMD) changes using dual energy X-ray absorptiometry (DXA) related to AI and BP treatment over a 12-month period. METHODS: Twenty seven postmenopausal breast cancer patients receiving AI therapy were recruited for this study. 22 subjects completed the 12-month study. 14 subjects received AI and BP (AI+BP), 8 subjects received AI without BP (AI-BP). All subjects underwent 3 T MRI. An eight-echo 3D spoiled gradient-echo sequence was used for CSE-based water-fat separation at the lumbar spine to generate PDFF maps. After manual segmentation of the vertebral bodies L1-L5 PDFF values were extracted for each vertebra and averaged for each subject. All subjects underwent DXA of the lumbar spine measuring the average BMD of L1-L4. RESULTS: Baseline age, PDFF and BMD showed no significant difference between the two groups (p > 0.05). There was a relative longitudinal increase in mean PDFF (∆relPDFF) in both groups (AI+BP: 5.93%; AI-BP: 3.11%) which was only significant (p = 0.006) in the AI+BP group. ∆relPDFF showed no significant difference between the two groups (p > 0.05). There was no significant longitudinal change in BMD (p > 0.05). CONCLUSIONS: Over a 12-month period, VBM PDFF assessed with CSE-MRI significantly increased in subjects receiving AI and BP. The present results contradict previous results regarding the effect of only BP therapy on bone marrow fat content quantified by magnetic resonance spectroscopy and bone biopsies. Future longer-term follow-up studies are needed to further characterize the effects of combined AI and BP therapy.

Optoacoustic properties of Doxorubicin - A pilot study.

Doxorubicin (DOX) is a widely used chemotherapeutic anticancer drug. Its intrinsic fluorescence properties enable investigation of tumor response, drug distribution and metabolism. First phantom studies in vitro showed optoacoustic property of DOX. We therefore aimed to further investigate the optoacoustic properties of DOX in biological tissue in order to explore its potential as theranostic agent. We analysed doxorubicin hydrochloride (Dox·HCl) and liposomal encapsulated doxorubicin hydrochloride (Dox·Lipo), two common drugs for anti-cancer treatment in clinical medicine. Optoacoustic measurements revealed a strong signal of both doxorubicin substrates at 488 nm excitation wavelength. Post mortem analysis of intra-tumoral injections of DOX revealed a detectable optoacoustic signal even at three days after the injection. We thereby demonstrate the general feasibility of doxorubicin detection in biological tissue by means of optoacoustic tomography, which could be applied for high resolution imaging at mesoscopic depths dictated by effective penetration of visible light into the biological tissues.