Cancer organoids to model therapy response: Cancer organoids are miniature, three-dimensional cell culture models that can be made from primary patient tumors and studied in the laboratory. Vlachogiannis et al. asked whether such “tumor-in-a-dish” approaches can be used to predict drug responses in the clinic. They generated a live organoid biobank from patients with metastatic gastrointestinal cancer who had previously been enrolled in phase I or II clinical trials. This allowed the authors to compare organoid drug responses with how the patient actually responded in the clinic. Encouragingly, the organoids had similar molecular profiles to those of the patient tumor, reinforcing their value as a platform for drug screening and development. Science , this issue p. 920

To prospectively determine whether dynamic contrast material-enhanced (DCE) magnetic resonance (MR) quantitative parameters correlate with fibrosis and microvascular density (MVD) in malignant and benign solid pancreatic focal lesions and nontumoral pancreatic tissue. The institutional review board approved the study; written informed consent was obtained. DCE MR was performed in 28 patients with surgically resectable focal pancreatic lesions. DCE MR quantitative parameters derived from one-compartment (OC) (transfer rate constant [K(trans)] and distribution fraction [ƒ]) and two-compartment (TC) (K(trans), tissue volume fraction occupied by extravascular extracellular space [v(i)], and tissue volume fraction occupied by vascular space [v(p)]) pharmacokinetic models were correlated with fibrosis content and MVD counts in focal lesions and nontumoral tissue (Spearman correlation coefficient [SCC]). Pharmacokinetic parameters were compared (Mann-Whitney test) between tumoral and nontumoral tissue. Diagnostic performance of DCE MR fibrosis detection was assessed (receiver operator characteristic curve analysis). K(trans) OC and K(trans) TC were significantly lower in primary malignant tumors compared with benign lesions (P = .023) and nontumoral pancreatic tissue downstream (P < .001) and upstream (P = .006); ƒ and v(i) were significantly higher in primary malignant tumors compared with nontumoral pancreatic tissue downstream (P = .012 and .018, respectively). Fibrosis was correlated negatively with K(trans) OC (SCC, -0.600) and K(trans) TC (SCC, -0.564) and positively with ƒ (SCC, 0.514) and v(i) (SCC, 0.464), with P < .001 (all comparisons). MVD was positively correlated with ƒ (SCC, 0.355; P = .019) and v(i) (SCC, 0.297; P = .038) but not with K(trans) OC (SCC, -0.140; P = .33) and K(trans) TC (SCC, -0.194; P = .181). Sensitivity and specificity for fibrosis detection were 65% (24 of 37) and 83% (10 of 12) for K(trans) OC (cutoff value, 0.35 min(-1)) and 76% (28 of 37) and 83% (10 of 12) for K(trans) TC (cutoff value, 0.29 min(-1)), respectively. Quantitative DCE MR parameters, derived from pharmacokinetic models in malignant and benign pancreatic solid lesions and nontumoral pancreatic tissue, were significantly correlated with fibrosis and MVD. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11103515/-/DC1.

To prospectively quantify pancreatic regional perfusion with dynamic contrast material-enhanced magnetic resonance (MR) imaging by using a one-compartment model and to assess perfusion changes during secretin stimulation in healthy volunteers. The study had institutional review board approval, and written informed consent was obtained. Ten healthy volunteers (five men, five women; mean age, 24.7 years +/- 1.9 [standard deviation]; range, 22-29 years) underwent MR imaging pancreatic perfusion studies performed twice without secretin and twice during secretin stimulation. Dynamic contrast-enhanced MR imaging consisted of saturation-recovery T1-weighted turbo-field-echo imaging with peripheral pulse triggering and respiratory tracking. A dose of 0.05 mmol gadodiamide per kilogram of body weight was injected at a rate of 3.5 mL/sec. Regional perfusion parameters were fitted with a one-compartment model. The analysis of variance test for repeated measurements was used to assess differences in pancreatic perfusion without and that with secretin administration. Significant differences in perfusion parameters between the three pancreatic regions were observed (P < .05). During secretin stimulation, a significant difference was observed only between the body and the tail of the pancreas (P = .02). A significant increase (P = .003) in pancreatic perfusion was observed after secretin administration. Mean pancreatic perfusion was 184 mL/min/100 g of tissue +/- 71, 207 mL/min/100 g +/- 77, and 230 mL/min/100 g +/- 87 without secretin and 342 mL/min/100 g +/- 154, 338 mL/min/100 g +/- 156, and 373 mL/min/100 g +/- 176 after secretin stimulation in the head, body, and tail of the pancreas, respectively. Intraindividual variability was 21% without secretin stimulation and 46% with secretin stimulation. Dynamic contrast-enhanced MR imaging enables noninvasive quantification of regional pancreatic perfusion in resting conditions and demonstrates the increase in pancreatic perfusion during secretin stimulation in healthy subjects.