Tumor classification of gastrointestinal liver metastases using CT-based radiomics and deep learning.

OBJECTIVES: The goal of this study is to demonstrate the performance of radiomics and CNN-based classifiers in determining the primary origin of gastrointestinal liver metastases for visually indistinguishable lesions. METHODS: In this retrospective, IRB-approved study, 31 pancreatic cancer patients with 861 lesions (median age [IQR]: 65.39 [56.87, 75.08], 48.4% male) and 47 colorectal cancer patients with 435 lesions (median age [IQR]: 65.79 [56.99, 74.62], 63.8% male) were enrolled. A pretrained nnU-Net performed automated segmentation of 1296 liver lesions. Radiomics features for each lesion were extracted using pyradiomics. The performance of several radiomics-based machine-learning classifiers was investigated for the lesions and compared to an image-based deep-learning approach using a DenseNet-121. The performance was evaluated by AUC/ROC analysis. RESULTS: The radiomics-based K-nearest neighbor classifier showed the best performance on an independent test set with AUC values of 0.87 and an accuracy of 0.67. In comparison, the image-based DenseNet-121-classifier reached an AUC of 0.80 and an accuracy of 0.83. CONCLUSIONS: CT-based radiomics and deep learning can distinguish the etiology of liver metastases from gastrointestinal primary tumors. Compared to deep learning, radiomics based models showed a varying generalizability in distinguishing liver metastases from colorectal cancer and pancreatic adenocarcinoma.

Combined non-invasive assessment of endothelial shear stress and molecular imaging of inflammation for the prediction of inflamed plaque in hyperlipidaemic rabbit aortas.

AIMS: To evaluate the incremental value of low endothelial shear stress (ESS) combined with high-resolution magnetic resonance imaging (MRI)- and computed tomography angiography (CTA)-based imaging for the prediction of inflamed plaque. METHODS AND RESULTS: Twelve hereditary hyperlipidaemic rabbits underwent quantitative analysis of plaque in the thoracic aorta with 256-slice CTA and USPIO-enhanced (ultra-small superparamagnetic nanoparticles, P904) 1.5-T MRI at baseline and at 6-month follow-up. Computational fluid dynamics using CTA-based 3D reconstruction of thoracic aortas identified the ESS patterns in the convex and concave curvature subsegments of interest. Subsegments with low baseline ESS exhibited significant increase in wall thickness and plaque inflammation by MRI, in non-calcified plaque burden by CTA, and developed increased plaque size, lipid and inflammatory cell accumulation (high-risk plaque features) at follow-up by histopathology. Multiple regression analysis identified baseline ESS and inflammation by MRI to be independent predictors of plaque progression, while receiver operating curve analysis revealed baseline ESS alone or in combination with inflammation by MRI as the strongest predictor for augmented plaque burden and inflammation (low ESS at baseline: AUC = 0.84, P < 0.001; low ESS and inflammation by molecular MRI at baseline: AUC = 0.89, P < 0.001). CONCLUSION: Low ESS predicts progression of plaque burden and inflammation as assessed by non-invasive USPIO-enhanced MRI. Combined non-invasive assessment of ESS and imaging of inflammation may serve to predict plaque with high-risk features.

Cochlear implantation in children with bacterial meningitic deafness: The influence of the degree of ossification and obliteration on impedance and charge of the implant.

OBJECTIVES: To determine impedance values and charge consumption following cochlear implantation post-meningitic deaf children depending on the grade of cochlear ossification and obliteration. METHODS: Post-meningitic deaf (n=49) and control (n=43) children treated with cochlear implants were included in the study. Impedance and charge values were calculated for each group. The degree of ossification of the cochlea was evaluated from a high-resolution computed tomography (HRCT) scan whereas the degree of obliteration was determined intraoperatively by the surgeon. RESULTS: Pneumococci were the principal pathogen responsible for bacterial meningitis, followed by meningococci. In HRCT scans, the degree of ossification was 1 and 2 in 29% of patients. The results of the intraoperative assessment of the cochlea showed obliteration grade 1 in 38% and grade 2 in 23% of cases. Children in the meningitis group showed significant higher impedances comparing to the control group. A significantly increased charge consumption was observed in patients with a grade 2 ossification when compared to those without ossification (P=0.02). Discussion Cochlea implanted children with meningitis-related deafness exhibit higher impedances, especially in the region of the basal and middle turn, however, not depending on the degree of cochlear ossification. High impedances and charge in the meningitis group may be explained by alterations in the central auditory pathway or on the electrode surface. CONCLUSION: To optimize the outcome in post-meningitic deaf children, surgery is advisable at an early stage prior to the onset of cochlear ossification.

Low dose tomographic fluoroscopy: 4D intervention guidance with running prior.

PURPOSE: Today's standard imaging technique in interventional radiology is the single- or biplane x-ray fluoroscopy which delivers 2D projection images as a function of time (2D+T). This state-of-the-art technology, however, suffers from its projective nature and is limited by the superposition of the patient's anatomy. Temporally resolved tomographic volumes (3D+T) would significantly improve the visualization of complex structures. A continuous tomographic data acquisition, if carried out with today's technology, would yield an excessive patient dose. Recently the authors proposed a method that enables tomographic fluoroscopy at the same dose level as projective fluoroscopy which means that if scanning time of an intervention guided by projective fluoroscopy is the same as that of an intervention guided by tomographic fluoroscopy, almost the same dose is administered to the patient. The purpose of this work is to extend authors' previous work and allow for patient motion during the intervention. METHODS: The authors propose the running prior technique for adaptation of a prior image. This adaptation is realized by a combination of registration and projection replacement. In a first step the prior is deformed to the current position via affine and deformable registration. Then the information from outdated projections is replaced by newly acquired projections using forward and backprojection steps. The thus adapted volume is the running prior. The proposed method is validated by simulated as well as measured data. To investigate motion during intervention a moving head phantom was simulated. Real in vivo data of a pig are acquired by a prototype CT system consisting of a flat detector and a continuously rotating clinical gantry. RESULTS: With the running prior technique it is possible to correct for motion without additional dose. For an application in intervention guidance both steps of the running prior technique, registration and replacement, are necessary. Reconstructed volumes based on the running prior show high image quality without introducing new artifacts and the interventional materials are displayed at the correct position. CONCLUSIONS: The running prior improves the robustness of low dose 3D+T intervention guidance toward intended or unintended patient motion.

Real-time X-ray-based 4D image guidance of minimally invasive interventions.

OBJECTIVE: A new technology is introduced that enables real-time 4D (three spatial dimensions plus time) X-ray guidance for vascular catheter interventions with acceptable levels of ionising radiation. METHODS: The enabling technology is a combination of low-dose tomographic data acquisition with novel compressed sensing reconstruction and use of prior image information. It was implemented in a prototype set-up consisting of a gantry-based flat detector system. In pigs (n = 5) angiographic interventions were simulated. Radiation dosage on a per time base was compared with the "gold standard" of X-ray projection imaging. RESULTS: Contrary to current image guidance methods that lack permanent 4D updates, the spatial position of interventional instruments could be resolved in continuous, spatial 4D guidance; the movement of the guide wire as well as the expansion of stents could be precisely tracked in 3D angiographic road maps. Dose rate was 23.8 µGy/s, similar to biplane standard angiographic fluoroscopy, which has a dose rate of 20.6 µGy/s. CONCLUSION: Real-time 4D X-ray image-guidance with acceptable levels of radiation has great potential to significantly influence the field of minimally invasive medicine by allowing faster and safer interventions and by enabling novel, much more complex procedures for vascular and oncological minimally invasive therapy. KEY POINTS: • Real-time 4D (three spatial dimensions plus time) angiographic intervention guidance is realistic. • Low-dose tomographic data acquisition with special compressed sensing-based algorithms is enabled. • Compared with 4D CT fluoroscopy, this method reduces radiation to acceptable levels. • Once implemented, vascular interventions may become safer and faster. • More complex intervention approaches may be developed.

Imaging of cardiac perfusion of free-breathing small animals using dynamic phase-correlated micro-CT.

PURPOSE: Mouse models of cardiac diseases have proven to be a valuable tool in preclinical research. The high cardiac and respiratory rates of free breathing mice prohibit conventional in vivo cardiac perfusion studies using computed tomography even if gating methods are applied. This makes a sacrification of the animals unavoidable and only allows for the application of ex vivo methods. METHODS: To overcome this issue the authors propose a low dose scan protocol and an associated reconstruction algorithm that allows for in vivo imaging of cardiac perfusion and associated processes that are retrospectively synchronized to the respiratory and cardiac motion of the animal. The scan protocol consists of repetitive injections of contrast media within several consecutive scans while the ECG, respiratory motion, and timestamp of contrast injection are recorded and synchronized to the acquired projections. The iterative reconstruction algorithm employs a six-dimensional edge-preserving filter to provide low-noise, motion artifact-free images of the animal examined using the authors' low dose scan protocol. RESULTS: The reconstructions obtained show that the complete temporal bolus evolution can be visualized and quantified in any desired combination of cardiac and respiratory phase including reperfusion phases. The proposed reconstruction method thereby keeps the administered radiation dose at a minimum and thus reduces metabolic inference to the animal allowing for longitudinal studies. CONCLUSIONS: The authors' low dose scan protocol and phase-correlated dynamic reconstruction algorithm allow for an easy and effective way to visualize phase-correlated perfusion processes in routine laboratory studies using free-breathing mice.

Image findings of patients with H1N1 virus pneumonia and acute respiratory failure.

RATIONALE AND OBJECTIVES: The aim of this study was to assess the findings of chest radiography and high-resolution computed tomography in patients requiring intensive care unit treatment for severe H1N1 virus pneumonia. MATERIALS AND METHODS: In 2009, 10 patients required treatment in an intensive care unit for confirmed H1N1 pneumonia. All patients underwent chest radiography and high-resolution computed tomography. All 10 patients required mechanical ventilation because of respiratory failure. Nine patients presented with severe acute respiratory distress syndrome, and one patient died. Four patients underwent extracorporeal membrane oxygenation (ECMO) therapy. The results of chest radiography and high-resolution computed tomographic scans of these patients were systematically analyzed. RESULTS: The mean age of all patients was 44.1 +/- 12.3 years. All 10 patients showed abnormal results on chest radiography. The radiographic abnormalities were bilateral and multifocal in 10 patients. The predominant radiographic findings were consolidations (n = 9), ground-glass opacities (n = 8), and reticular opacities (n = 2). The most frequent computed tomographic findings at presentation consisted of bilateral ground-glass opacities (n = 9), pleural effusion (n = 9), areas of consolidation (n = 8), interstitial marking (n = 8), and crazy paving (n = 4). All patients undergoing ECMO therapy showed extensive bilateral ground-glass opacities, multifocal areas of consolidation, and crazy paving. Pleural effusion was present in three of four patients undergoing ECMO therapy. CONCLUSION: Patients requiring treatment in an intensive care unit for severe H1N1 pneumonia are at high risk for developing acute respiratory distress syndrome and frequently require ECMO therapy.

Anti-CD4-targeted gold nanoparticles induce specific contrast enhancement of peripheral lymph nodes in X-ray computed tomography of live mice.

Antibody-conjugated gold nanoparticles have been applied as a biologically targeted contrast agent in live mice for one of the most widely used medical imaging methods, X-ray computed tomography. Such nanoprobes directed toward the CD4 receptor lead to distinctly enhanced X-ray contrast of peripheral lymph nodes. This study demonstrates the general feasibility of biologically specific X-ray imaging in living animals and discusses basic requirements for the use of nanoparticles as a targeted X-ray contrast agent.

Resistance to antiangiogenic therapy is directed by vascular phenotype, vessel stabilization, and maturation in malignant melanoma.

Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor beta, and the late-stage maturity marker alpha smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this.

Imaging anti-angiogenic treatment response with DCE-VCT, DCE-MRI and DWI in an animal model of breast cancer bone metastasis.

As current classification systems for the assessment of treatment response in bone metastasis do not meet the needs of oncologists, new imaging biomarkers are desirable. Therefore, the diagnostic impact of dynamic contrast enhanced (DCE)-volumetric computed tomography (VCT) (descriptive analysis), DCE-MRI (two-compartment model) and diffusion weighted imaging (DWI) for monitoring anti-angiogenic therapy effects of the VEGF antibody bevacizumab in breast cancer bone metastases in rats was studied. Nude rats (n=8 animals treated with bevacizumab and n=9 untreated control rats) with site-specific osteolytic bone metastasis of the hind leg were imaged with a 1.5T clinical MRI-scanner in an animal coil as well as in a volumetric CT-scanner at days 30, 40, 50 and 60 after inoculation of MDA-MB-231 human breast cancer cells. From these data, osteolytic lesion size (OLS), peak enhancement (PE), area under the curve (AUC), amplitude (A), exchange rate constant (k(ep)) and apparent diffusion coefficient (ADC) were determined in bone metastases. Prior to changes in OLS (p< or =0.05 at days 50 and 60) there was already a significant decrease in PE, AUC and A (p< or =0.05 at days 40-60) in treated animals compared to controls. However, for k(ep) and ADC there were no significant differences between the groups at any time point (p>0.05 at days 40-60). In conclusion, anti-angiogenic treatment response in osteolytic breast cancer bone metastases can be assessed early with surrogate markers of vascularization, while DWI appears to be insensitive.

A robot-guided minimally invasive approach for cochlear implant surgery: preliminary results of a temporal bone study.

PURPOSE: The aim of this study was to create an access canal to the inner ear, by drilling, and perform the cochleostomy for cochlear implant surgery using robot guidance. METHODS: A robot, a surgical drill and an Image-Guided Surgery (IGS) system were combined in a closed-loop setup. Ten temporal bones were scanned at the planning stages of the procedure. The robot guided the drill along the preplanned trajectory and created the approach. Postoperative scans were obtained. RESULTS: The cochleostomy was performed completely in nine out of ten cases. This did not prove possible for one of the specimens, the target site selected being in too superficial a location in relation to the round window. No violation of the facial nerve took place, although the chorda tympani nerve was violated in one case and the stapes in two. It was obvious during preoperative planning that these structures would be violated, but this was accepted in order to maintain a safety margin from the facial nerve. No other unforeseen damage occurred. CONCLUSIONS: This preliminary study suggests that robot-guided drilling of a minimally invasive approach to the cochlea might be feasible, but further improvements are necessary before any clinical application becomes possible. Where the width of the facial recess is less than 2.5 mm, the chorda tympani nerve and the ossicles are at risk.

Radiopaque iodinated copolymeric nanoparticles for X-ray imaging applications.

Recently we described iodinated homopolymeric radiopaque nanoparticles of 28.9+/-6.3 nm dry diameter synthesized by emulsion polymerization of 2-methacryloyloxyethyl(2,3,5-triiodobenzoate) (MAOETIB). The nanoparticle aqueous dispersion, however, was not stable and tended to agglomerate, particularly at weight concentration of dispersed nanoparticles above approximately 0.3%. The agglomeration rate increases as the concentration of nanoparticles in aqueous phase rises and prevents the potential in vivo use as contrast agent for medical X-ray imaging. Here we describe efforts to overcome this limitation by synthesis of iodinated copolymeric nanoparticles of 25.5+/-4.2 nm dry diameter, by emulsion copolymerization of the monomer, MAOETIB, with a low concentration of glycidyl methacrylate (GMA). The surface of resulting copolymeric nanoparticles is far more hydrophilic than that of polyMAOETIB (PMAOETIB) nanoparticles. Therefore, P(MAOETIB-GMA) nanoparticles are significantly more stable against agglomeration in aqueous continuous phase. After intravenous injection of P(MAOETIB-GMA) nanoparticles in rats and mice (including those with a liver cancer model) CT-imaging revealed a significant enhanced visibility of the blood pool for 30 min after injection. Later, lymph nodes, liver and spleen strongly enhanced due to nanoparticle uptake by the reticuloendothelial system. This favorably enabled the differentiation of cancerous from healthy liver tissue and suggests our particles for tumor imaging in liver and lymph nodes.

A mouse model for congenital myasthenic syndrome due to MuSK mutations reveals defects in structure and function of neuromuscular junctions.

In the muscle-specific tyrosine kinase receptor gene MUSK, a heteroallelic missense and a null mutation were identified in a patient suffering from a congenital myasthenic syndrome (CMS). We generated one mouse line carrying the homozygous missense mutation V789M in musk (musk(V789M/V789M) mice) and a second hemizygous line, resembling the patient genotype, with the V789M mutation on one allele and an allele lacking the kinase domain (musk(V789M/-) mice). We report here that musk(V789M/V789M) mice present no obvious abnormal phenotype regarding weight, muscle function and viability. In contrast, adult musk(V789M/-) mice suffer from severe muscle weakness, exhibit shrinkage of pelvic and scapular regions and hunchback. Musk(V789M/-) diaphragm develops less force upon direct or nerve-induced stimulation. A profound tetanic fade is observed following nerve-evoked muscle contraction, and fatigue resistance is severely impaired upon a train of tetanic nerve stimulations. Electrophysiological measurements indicate that fatigable muscle weakness is due to impaired neurotransmission as observed in a patient suffering from a CMS. The diaphragm of adult musk(V789M/-) mice exhibits pronounced changes in endplate architecture, distribution and innervation pattern. Thus, the missense mutation V789M in MuSK acts as a hypomorphic mutation and leads to insufficiency in MuSK function in musk(V789M/-) mutants. These mutant mice represent valuable models for elucidating the roles of MuSK for synapse formation, maturation and maintenance as well as for studying the pathophysiology of a CMS due to MuSK mutations.

Bevacizumab inhibits breast cancer-induced osteolysis, surrounding soft tissue metastasis, and angiogenesis in rats as visualized by VCT and MRI.

The aim of this study was to evaluate the effect of an antiangiogenic treatment with the vascular endothelial growth factor antibody bevacizumab in an experimental model of breast cancer bone metastasis and to monitor osteolysis, soft tissue tumor, and angiogenesis in bone metastasis noninvasively by volumetric computed tomography (VCT) and magnetic resonance imaging (MRI). After inoculation of MDA-MB-231 human breast cancer cells into nude rats, bone metastasis was monitored with contrast-enhanced VCT and MRI from day 30 to day 70 after tumor cell inoculation, respectively. Thereby, animals of the treatment group (10 mg/kg bevacizumab IV weekly, n = 15) were compared with sham-treated animals (n = 17). Treatment with bevacizumab resulted in a significant difference versus control in osteolytic as well as soft tissue lesion sizes (days 50 to 70 and 40 to 70 after tumor cell inoculation, respectively; P < .05). This observation was paralleled with significantly reduced vascularization in the treatment group as shown by reduced increase in relative signal intensity in dynamic contrast-enhanced MRI from days 40 to 70 (P < .05). Contrast-enhanced VCT and histology confirmed decreased angiogenesis as well as new bone formation after application of bevacizumab. In conclusion, bevacizumab significantly inhibited osteolysis, surrounding soft tissue tumor growth, and angiogenesis in an experimental model of breast cancer bone metastasis as visualized by VCT and MRI.

Virtual endoscopy of the middle ear: experimental and clinical results of a standardised approach using multi-slice helical computed tomography.

Virtual endoscopy (VE) enables non-invasive 3D endoluminal imaging of the middle ear by post-processing of CT data. To optimise the clinical application a standardised approach was evaluated in normal and pathologic cases. Data acquisition was performed using multi-slice helical CT in 20 normal patients and 15 patients with malformation or trauma. Virtual endoscopy of the tympanic cavity and 3D images of the ossicles were generated using surface and volume rendering. Qualitative assessment of the representation of anatomical structures was performed in normal patients. In 15 pathological cases the diagnostic benefit was evaluated by comparing the 3D images to the 2D images and intra-operative findings. In all 35 cases 3D imaging was possible using the standardised approach. The ossicular chain as well as the bony and soft tissue structures of the tympanic cavity were visualised in 20 normal patients. In 7 of 8 patients with malformation and 1 of 7 patients with trauma the original diagnosis was changed by 3D imaging. Standardisation and evaluation of the method in normal patients is essential as it enhances the diagnostic reliability. Virtual endoscopy facilitates understanding of the complex anatomy of the middle ear. In cases of suspected malformation and confirmed trauma it is helpful for diagnosis and surgical planning.