Ist milde Hyperthermie in der Lage Desmoplasie in Pankreastumoren aufzulösen?: Untersuchungen an einem in vitro Modell

Pankreaskarzinome haben unter den häufigen Tumoren die schlechteste Prognose. Diese ist unter anderem auf den hohen Stromaanteil zurückzuführen, den man als Desmoplasie bezeichnet. Dadurch bedingt werden Tumorgefäße komprimiert, sodass systemisch applizierte Chemotherapeutika die Tumorzellen nur unzureichend erreichen. Da Wärme bekanntermaßen sowohl eine proteindenaturierende als auch eine zytotoxische Wirkung hat, kann diese eine vielversprechende Möglichkeit zur Auflösung der Desmoplasie und zur Zellreduktion darstellen. Trotz dieser Erkenntnisse ist die Wirkung einer Hyperthermie auf das Tumorstroma nur unzureichend geklärt. Die vorliegende Arbeit untersucht daher, den Einfluss einer Hyperthermie auf das Tumorstroma und die Zellen von Pankreaskarzinomen. Zunächst wurden an murinen Kollagenquellen kollagendegradierende Temperaturen im Bereich der milden Hyperthermie ermittelt. Weiterhin wurden Tumorzellsphäroide aus Pankreaskarzinomzellen und Fibroblasten gebildet, welche die Desmoplasie nachbilden sollen. Diese wurden einstündig mit den zuvor ermittelten Temperaturen behandelt. Nach der Wärmeexposition wurden die Auswirkungen der Hyperthermie auf die Integrität der Kollagenfasern mittels Second Harmonic Generation-Mikroskopie analysiert. Die Wirkung stromadegradierender Temperaturen auf die Vitalität von Tumorzellen wurde fluoreszenzmikrokopisch bestimmt. In der Arbeit konnte gezeigt werden, dass die Behandlung der Sphäroide mit den zuvor ermittelten kollagendegradierenden Temperaturen von 40 °C und 42 °C eine Reduktion intakter Kollagenfasern um 90 % bewirkte. Zudem ergab die Hyperthermie eine signifikante Reduktion vitaler Zellen. Zusammenfassend konnte gezeigt werden, dass eine milde Hyperthermie die Desmoplasie reduzieren und letale Effekte induzieren kann, sodass eine Hyperthermiebehandlung das Therapieansprechen von Pankreaskarzinomen auf additiv verabreichte Chemotherapie durch Dekompression von Tumorgefäßen verbessern könnte

Reproducibility of pulmonary magnetic resonance angiography in adults with muco-obstructive pulmonary disease

Background Recent studies support magnetic resonance angiography (MRA) as a diagnostic tool for pulmonary arterial disease. Purpose To determine MRA image quality and reproducibility, and the dependence of MRA image quality and reproducibility on disease severity in patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Material and Methods Twenty patients with COPD (mean age 66.5 ± 8.9 years; FEV1% = 42.0 ± 13.3%) and 15 with CF (mean age 29.3 ± 9.3 years; FEV1% = 66.6 ± 15.8%) underwent morpho-functional chest magnetic resonance imaging (MRI) including time-resolved MRA twice one month apart (MRI1, MRI2), and COPD patients underwent non-contrast computed tomography (CT). Image quality was assessed visually using standardized subjective 5-point scales. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were measured by regions of interest. Disease severity was determined by spirometry, a well-evaluated chest MRI score, and by computational CT emphysema index (EI) for COPD. Results Subjective image quality was diagnostic for all MRA at MRI1 and MRI2 (mean score = 4.7 ± 0.6). CNR and SNR were 4 43.8 ± 8.7 and 50.5 ± 8.7, respectively. Neither image quality score nor CNR or SNR correlated with FEV1% or chest MRI score for COPD and CF (r = 0.239–0.248). CNR and SNR did not change from MRI1 to MRI2 (P = 0.434–0.995). Further, insignificant differences in CNR and SNR between MRA at MRI1 and MRI2 did not correlate with FEV1% nor chest MRI score in COPD and CF (r = −0.238–0.183), nor with EI in COPD (r = 0.100–0.111). Conclusion MRA achieved diagnostic quality in COPD and CF patients and was highly reproducible irrespective of disease severity. This supports MRA as a robust alternative to CT in patients with underlying muco-obstructive lung disease

Iterative Metal Artifact Reduction (iMAR) of the Non-adhesive Liquid Embolic Agent Onyx in Computed Tomography

Background!#!A drawback of Onyx, one of the most used embolic agents for endovascular embolization of intracranial arteriovenous malformations (AVM), is the generation of imaging artifacts (IA) in computed tomography (CT). Since these artifacts can represent an obstacle for the detection of periprocedural bleeding, this study investigated the effect of artifact reduction by an iterative metal artifact reduction (iMAR) software in CT in a brain phantom.!##!Methods!#!Two different in vitro models with two-dimensional tube and three-dimensional AVM-like configuration were filled with Onyx 18. The models were inserted into a brain imaging phantom and images with (n = 5) and without (n = 10) an experimental hemorrhage adjacent were acquired. Afterwards, the iMAR algorithm was applied for artifact reduction. The IAs of the original and the post-processed images were graded quantitatively and qualitatively. Moreover, qualitative definition of the experimental hemorrhage was investigated.!##!Results!#!Comparing the IAs of the original and the post-processed CT images, quantitative and qualitative analysis showed a lower degree of IAs in the post-processed images, i.e. quantitative analysis: 2D tube model: 23.92 ± 8.02 Hounsfield units (HU; no iMAR; mean ± standard deviation) vs. 5.93 ± 0.43 HU (with iMAR; p < 0.001); qualitative analysis: 3D AVM model: 4.93 ± 0.18 vs. 3.40 ± 0.48 (p < 0.001). Furthermore, definition of the experimental hemorrhage was better in the post-processed images of both in vitro models (2D tube model: p = 0.004; 3D AVM model: p = 0.002).!##!Conclusion!#!The iMAR algorithm can significantly reduce the IAs evoked by Onyx 18 in CT. Applying iMAR could thus improve the accuracy of postprocedural CT imaging after embolization with Onyx in clinical practice

Sine Spin flat detector CT can improve cerebral soft tissue imaging: a retrospective in vivo study

Abstract Background Flat detector computed tomography (FDCT) is frequently applied for periinterventional brain imaging within the angiography suite. Novel technical developments such as the Sine Spin FDCT (S-FDCT) may provide an improved cerebral soft tissue contrast. This study investigates the effect of S-FDCT on the differentiation between gray and white matter compared to conventional FDCT (C-FDCT) and multidetector computed tomography (MDCT). Methods A retrospective analysis of a prospectively maintained patient database was performed, including patients who underwent mechanical thrombectomy in our institution and received S-FDCT or C-FDCT as well as MDCT. Differentiation between gray and white matter on the contralateral hemisphere to the ischemic stroke was analyzed quantitatively by contrast-to-noise ratio (CNR) and qualitatively (5-point ordinal scale). Results In a cohort of 109 patients, MDCT demonstrated the best differentiation between gray and white matter compared to both FDCT techniques (p ≤ 0.001). Comparing both generations of FDCT, S-FDCT provided better visibility of the basal ganglia (p = 0.045) and the supratentorial cortex (p = 0.044) compared to C-FDCT both in quantitative and qualitative analyses. Median CNR were as follows: S-FDCT 2.41 (interquartile range [IQR] 1.66–3.21), C-FDCT 0.96 (0.46–1.70), MDCT 3.43 (2.83–4.17). For basal ganglia, median score and IQR were as follows: S-FDCT 2.00 (2.00–3.00), C-FDCT 1.50 (1.00–2.00), MDCT 5.00 (4.00–5.00). Conclusions The novel S-FDCT improves the periinterventional imaging quality of cerebral soft tissue compared to C-FDCT. Thus, it may improve the diagnosis of complications within the angiography suite. MDCT provides the best option for x-ray-based imaging of the brain tissue. Relevance statement Flat detector computed tomography is a promising technique for cerebral soft tissue imaging, while the novel Sine Spin flat detector computed tomography technique improves imaging quality compared to conventional flat detector computed tomography and thus may facilitate periinterventional diagnosis of gray and white matter. Key points • Flat detector computed tomography (FDCT) is frequently applied for periinterventional brain imaging. • The potential of novel Sine Spin FDCT (S-FDCT) is unknown so far. • S-FDCT improves the visibility of cerebral soft tissue compared to conventional FDCT. • Multidetector computed tomography is superior to both FDCT techniques. • S-FDCT may facilitate the evaluation of brain parenchyma within the angiography suite. Graphical Abstrac