IntroductionIn brain perfusion imaging, arterial spin labeling (ASL) is a noninvasive alternative to dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI). For clinical imaging, only product sequences can be used. We therefore analyzed the performance of a product sequence (PICORE-PASL) included in an MRI software-package compared with DSC-MRI in patients with steno-occlusion of the MCA or ICA >70%.MethodsImages were acquired on a 3T MRI system and qualitatively analyzed by 3 raters. For a quantitative analysis, cortical ROIs were placed in co-registered ASL and DSC images. Pooled data for ASL-cerebral blood flow (CBF) and DSC-CBF were analyzed by Spearman’s correlation and the Bland-Altman (BA)-plot.ResultsIn 28 patients, 11 ASL studies were uninterpretable due to patient motion. Of the remaining patients, 71% showed signs of delayed tracer arrival. A weak correlation for DSC-relCBF vs ASL-relCBF (r = 0.24) and a large spread of values in the BA-plot owing to unreliable CBF-measurement was found.ConclusionThe PICORE ASL product sequence is sensitive for estimation of delayed tracer arrival, but cannot be recommended to measure CBF in steno-occlusive disease. ASL-sequences that are less sensitive to patient motion and correcting for delayed blood flow should be available in the clinical setting.
Pulsed arterial spin labeling (PASL) at multiple inflow times (multi-TIs) is advantageous for the measurement of brain perfusion in patients with long arterial transit times (ATTs) as in steno-occlusive disease, because bolus-arrival-time can be measured and blood flow measurements can be corrected accordingly. Owing to its increased signal-to-noise ratio, a combination with a three-dimensional gradient and spin echo (GRASE) readout allows acquiring a sufficient number of multi-TIs within a clinically feasible acquisition time of 5 minutes. We compared this technique with the clinical standard dynamic susceptibility-weighted contrast-enhanced imaging-magnetic resonance imaging in patients with unilateral stenosis >70% of the internal carotid or middle cerebral artery (MCA) at 3 Tesla. We performed qualitative (assessment by three expert raters) and quantitative (region of interest (ROI)/volume of interest (VOI) based) comparisons. In 43 patients, multi-TI PASL-GRASE showed perfusion alterations with moderate accuracy in the qualitative analysis. Quantitatively, moderate correlation coefficients were found for the MCA territory (ROI based: r=0.52, VOI based: r=0.48). In the anterior cerebral artery (ACA) territory, a readout related right-sided susceptibility artifact impaired correlation (ROI based: r=0.29, VOI based: r=0.34). Arterial transit delay artifacts were found only in 12% of patients. In conclusion, multi-TI PASL-GRASE can correct for arterial transit delay in patients with long ATTs. These results are promising for the transfer of ASL to the clinical practice.
BackgroundThe lack of predictive biomarkers or test systems contributes to high failure rates of systemic therapy in metastasized colorectal carcinoma, accounting for a still unfavorable prognosis. Here, we present an ex vivo functional assay to measure drug-response based on a tissue slice culture approach.MethodsTumor tissue slices of hepatic metastases of nine patients suffering from colorectal carcinoma were cultivated for 72 h and treated with different concentrations of the clinically relevant drugs Oxaliplatin, Cetuximab and Pembrolizumab. Easy to use, objective and automated analysis routines based on the Halo platform were developed to measure changes in proliferative activity and the morphometric make-up of the tumor. Apoptotic indices were assessed semiquantitatively.ResultsUntreated tumor tissue slices showed high morphological comparability with the original “in vivo”-tumor, preserving proliferation and stromal-tumor interactions. All but one patients showed a dosage dependent susceptibility to treatment with Oxaliplatin, whereas only two patients showed responses to Cetuximab and Pembrolizumab, respectively. Furthermore, we identified possible non-responders to Cetuximab therapy in absence of RAS-mutations.ConclusionsThis is the first time to demonstrate feasibility of the tissue slice culture approach for metastatic tissue of colorectal carcinoma. An automated readout of proliferation and tumor-morphometry allows for quantification of drug susceptibility. This strongly indicates a potential value of this technique as a patient-specific test-system of targeted therapy in metastatic colorectal cancer. Co-clinical trials are needed to customize for clinical application and to define adequate read-out cut-off values.
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