scholarly journals Timeliness of splenic time-to-peak affects liver tumor CT perfusion measurements

Author(s):  
Rajeev Hatwar ◽  
Sahar Mirpour ◽  
Anilchandra Attaluri ◽  
J. Webster Stayman ◽  
Robert Ivkov ◽  
...  

Abstract Aim In liver CT perfusion, the dual-input maximum slope (DI-MS) method is commonly used to estimate perfusion to aid diagnosis of tumors. The DI-MS method relies on a model that assumes the splenic time-to-peak (TTP) separates arterial and portal venous perfusion, and occurs prior to venous perfusion. In this preclinical study, we examined how the timeliness of splenic TTP affects DI-MS perfusion calculations of liver tumors. Materials and Methods We analyzed imaging data obtained from 11 New Zealand White rabbits bearing a single implanted VX2 tumor in liver. A liver 320-slice CT perfusion protocol (5,400 images per study) was used to generate images. Times for arterial and portal slopes were recorded, and hepatic arterial perfusion (HAP), portal perfusion (HPP) and perfusion index (HPI) for liver and tumor were separately calculated using manual and automated methods. T-test comparisons and Bland-Altman plot analyses were performed. Results Mean tumor TTP occurred at 9.79 s (SD=3.41) and splenic TTP at 9.75 s (SD=4.47, p=0.98). In 3/11 (27.27%) cases, tumor SP occurred prior to spleen (mean difference=1.33 s, SD=1.15 s). In these cases, mean automated HPP values were 43.8% (SD=52.48) higher compared to manually computed ones. There were statistically significant differences between automated and manual methods for normal liver and tumor HPI and HPP (p<0.01 and p<0.0001, respectively), but not HAP values (p=0.125 and p=0.78, respectively). There was also a statistically significant variation between methods for tumor HPP and HPI (p=0.001, respectively). Conclusion In 320-slice CT perfusion of liver in this preclinical model, we observed that tumor TTP occurred prior to splenic TTP in 27.27% of tumors in liver. This temporal relationship affects tumor perfusion calculations and should be identified to address potential deviations of model assumptions.

2012 ◽  
Vol 36 (4) ◽  
pp. 388-393 ◽  
Author(s):  
Chaan S. Ng ◽  
Adam G. Chandler ◽  
Wei Wei ◽  
Ella F. Anderson ◽  
Delise H. Herron ◽  
...  

Radiology ◽  
2011 ◽  
Vol 260 (3) ◽  
pp. 762-770 ◽  
Author(s):  
Chaan S. Ng ◽  
Adam G. Chandler ◽  
Wei Wei ◽  
Delise H. Herron ◽  
Ella F. Anderson ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1537
Author(s):  
Stephan Walrand ◽  
Michel Hesse ◽  
Philippe d’Abadie ◽  
François Jamar

Liver radioembolization is a treatment option for unresectable liver cancers, performed by infusion of 90Y or 166Ho loaded spheres in the hepatic artery. As tumoral cells are mainly perfused via the liver artery unlike hepatic lobules, a twofold tumor to normal liver dose ratio is commonly obtained. To improve tumoral cell killing while preserving lobules, co-infusion of arterial vasoconstrictor has been proposed but with limited success: the hepatic arterial buffer response (HABR) and hepatic vascular escape mechanism hamper the arterioles vasoconstriction. The proposed project aims to take benefit from the HABR by co-infusing a mesenteric arterial vasodilator: the portal flow enhancement inducing the vasoconstriction of the intra sinusoids arterioles barely impacts liver tumors that are mainly fed by novel and anarchic external arterioles. Animal studies were reviewed and dopexamine was identified as a promising safe candidate, reducing by four the hepatic lobules arterial flow. A clinical trial design is proposed. A four to sixfold improvement of the tumoral to normal tissue dose ratio is expected, pushing the therapy towards a real curative intention, especially in HCC where ultra-selective spheres delivery is often not possible.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kai Scherer ◽  
Johannes Hammel ◽  
Thorsten Sellerer ◽  
Korbinian Mechlem ◽  
Bernhard Renger ◽  
...  

Abstract Ischemic heart disease is the globally leading cause of death. When using coronary CT angiography, the functional hemodynamics within the myocardium remain uncertain. In this study myocardial CT perfusion imaging using iodine contrast agent demonstrated to strongly improve the assessment of myocardial disorders. However, a retrieval of such dynamics using Hounsfield units from conventional CT poses concerns with respect to beam-hardening effects and low contrast-to-noise ratio (CNR). Dual-energy CT offers novel approaches to overcome aforementioned limitations. Quantitative peak enhancement, perfusion, time to peak and iodine volume measurements inside the myocardium were determined resulting in 0.92 mg/ml, 0.085 mg/ml/s 17.12 s and 29.89 mg/ml*s, respectively. We report on the first extensive quantitative and iodine-based analysis of myocardial dynamics in a healthy porcine model using a dual-layer spectral CT. We further elucidate on the potential of reducing the radiation dose from 135 to 18 mGy and the contrast agent volume from 60 to 30 mL by presenting a two-shot acquisition approach and measuring iodine concentrations in the myocardium in-vivo down to 1 mg/ml, respectively. We believe that dynamic quantitative iodine perfusion imaging may be a highly sensitive tool for the precise functional assessment and monitoring of early myocardial ischemia.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Bruce C Campbell ◽  
Søren Christensen ◽  
Christopher R Levi ◽  
Patricia M Desmond ◽  
Geoffrey A Donnan ◽  
...  

Background and purpose: CT-perfusion (CTP) is widely and rapidly accessible for imaging acute ischemic stroke. However, there has been limited validation of CTP parameters against the more intensively studied MRI perfusion-diffusion mismatch paradigm. We tested the correspondence of CTP with contemporaneous perfusion-diffusion MRI. Methods: Acute ischemic stroke patients <6hr after onset had CTP and perfusion-diffusion MRI within 1hr, before reperfusion therapies. Relative cerebral blood flow (relCBF) and time-to-peak of the deconvolved tissue-residue-function (Tmax) were calculated (standard singular value decomposition deconvolution). The diffusion lesion was registered to the CTP slabs and manually outlined to its maximal visual extent. CT-infarct core was defined as relCBF<31% contralateral mean as previously published using this software. The volumetric accuracy of relCBF core compared to the diffusion lesion was tested in isolation, but also when restricted to pixels with relative time-to-peak (TTP) >4sec, to reduce artifactual false positive low CBF (eg in leukoaraiosis). The MR Tmax>6sec perfusion lesion (previously validated to define penumbral tissue at risk of infarction) was automatically segmented and registered to the CTP slabs. Receiver operating characteristic (ROC) analysis determined the optimal CT-Tmax threshold to match MR-Tmax>6sec, confidence intervals generated by bootstrapping. Agreement of these CT parameters with MR perfusion-diffusion mismatch on co-registered slabs was assessed (mismatch ratio >1.2, absolute mismatch>10mL, infarct core<70mL). Results: In analysis of 98 CTP slabs (54 patients, median onset to CT 190min, median CT to MR 30min), volumetric agreement with the diffusion lesion was substantially improved by constraining relCBF<31% within the automated TTP perfusion lesion ROI (median magnitude of volume difference 9.0mL vs unconstrained 13.9mL, p<0.001). ROC analysis demonstrated the best CT-Tmax threshold to match MR-Tmax>6sec was 6.2sec (95% confidence interval 5.6-7.3sec, ie not significantly different to 6sec), sensitivity 91%, specificity 70%, AUC 0.87. Using CT-Tmax>6s “penumbra” and relCBF<31% (restricted to TTP>4s) “core”, volumetric agreement was sufficient for 90% concordance between CT and MRI-based mismatch status (kappa 0.80). Conclusions: Automated CTP mismatch classification using relCBF and Tmax is similar to perfusion-diffusion MRI. CTP may allow more widespread application of the “mismatch” paradigm in clinical practice and trials.


2018 ◽  
Author(s):  
Δημήτριος-Κώστας Ματσαρίδης

H μελέτη αξιολόγησε την πιθανή προοπτική της Δυναμικής Μαγνητικής Τομογραφίας (ΔΜΤ) του οστικού μυελού στο πολλαπλό μυέλωμα να διαδραματίσει το ρόλο ανεξάρτητου προγνωστικού παράγοντα στην εκτίμηση της βαρύτητας της νόσου, στην πρόβλεψη της κλινικής πορείας αλλά και της ανταπόκρισης στη θεραπευτική αγωγή.Υλικό-Μέθοδοι: Μελετήθηκαν 60 ασθενείς με πρωτοδιαγνωσθέν πολλαπλό μυέλωμα με Μαγνητική Τομογραφία (ΜΤ) του οστικού μυελού, προ της ενάρξεως της θεραπευτικής αγωγής. Κάθε ασθενής υποβλήθηκε σε συμβατική και ΔΜΤ της θωρακοοσφυϊκής μοίρας της σπονδυλικής στήλης και της πυέλου σε Μαγνητικό Τομογράφο 1,5Τ. Η συμβατική ΜΤ περιλάμβανε εγκάρσιες και οβελιαίες ακολουθίες Τ1 και Τ2 προσανατολισμού, DWI και STIR. H ΔΜΤ έγινε με λήψη 5 οβελιαίων τομών T1 προσανατολισμού μετά την ενδοφλέβια χορήγηση σκιαγραφικού μέσου, με επανάληψή τους κάθε 15 δευτερόλεπτα για συνολικό χρονικό διάστημα 3 λεπτών και 30 δευτερολέπτων.Από τα δεδομένα της δυναμικής ΜΤ προέκυψαν και επεξεργάστηκαν με ειδικό λογισμικό καμπύλες σκιαγραφικής ενίσχυσης του μυελού των οστών σε συνάρτηση με τον χρόνο. Τα ευρήματα της συμβατικής ΜΤ και οι παράμετροι αιμάτωσης που εξήχθησαν από τις καμπύλες έντασης σήματος-χρόνου της ΔΜΤ [WIN (maximum wash-in rate), WOUT (maximum wash-out rate), TTPK (time to peak enhancement), DCEmax (maximum peak enhancement), TMSP (time to maximum slope)] συσχετίστηκαν με τους γνωστούς δείκτες βαρύτητας της νόσου καθώς και παράγοντες αγγειογένεσης με σκοπό την αξιολόγηση της ΔΜΤ ως ανεξάρτητου μέσου εκτίμησης της βαρύτητας της νόσου και της πρόγνωσης αυτής.Αποτελέσματα-Συμπεράσματα: Διαπιστώθηκε πως στην ομάδα των συμπτωματικών ασθενών σημειώθηκαν αυξημένες τιμές WIN σε σύγκριση με την ομάδα των ασυμπτωματικών (p < 0,05) και την ομάδα των ασθενών με MGUS (p = 0,001). Το TTPK ήταν μειωμένο και το κλάσμα WIN/TMSP αυξημένο τόσο στους συμπτωματικούς και τους ασυμπτωματικούς σε σύγκριση με την ομάδα των ασθενών με MGUS (p < 0,05). Οι συμπτωματικοί ασθενείς με ΠΜ είχαν χαμηλότερες τιμές TMSP σε σχέση με τους ασθενείς με MGUS. Ο λόγος Angp-1/Angp-2 ήταν μειωμένος στους συμπτωματικούς συγκριτικά με τους ασυμπτωματικούς (p = 0,017) και στους ασθενείς με MGUS (p < 0,001). Το TTPK συσχετίστηκε με το λόγο Angp-1/Angp-2 όπως και με το στάδιο R-ISS. Ασθενείς με στάδιο R-ISS-3 είχαν χαμηλότερες διάμεσες τιμές TTPK (23 s, όριο διακύμανσης 18–29 s) συγκριτικά με ασθενείς με R-ISS-2 (48 s, όριο διακύμανσης 27–68 s) και ασθενείς με R-ISS-1 (54 s, όριο διακύμανσης 42–76 , p ANOVA = 0,01). Μια υποομάδα ασθενών με χαμηλό TTPK (κατώτερο τεταρτημόριο) εμφάνιζαν νωρίτερα πρόοδο της νόσου συγκριτικά με όλους τους υπόλοιπους ασθενείς.Τα ανωτέρω δεδομένα δείχνουν μια σαφή συσχέτιση ορισμένων εκ των παραμέτρων της ΔΜΤ με το στάδιο της νόσου κατά R-ISS καθώς και με αρνητικούς προγνωστικούς παράγοντες της νόσου όπως ο λόγος των αγγειογενετικών κυτοκινών (Angp-1/Angp-2).


Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3585
Author(s):  
Charly Helaine ◽  
Aurélie E. Ferré ◽  
Marine M. Leblond ◽  
Elodie A. Pérès ◽  
Myriam Bernaudin ◽  
...  

(1) We wanted to assess the impact of Ang2 in RCT-induced changes in the environment of glioblastoma. (2) The effect of Ang2 overexpression in tumor cells was studied in the GL261 syngeneic immunocompetent model of GB in response to fractionated RCT. (3) We showed that RCT combined with Ang2 led to tumor clearance for the GL261-Ang2 group by acting on the tumor cells as well as on both vascular and immune compartments. (4) In vitro, Ang2 overexpression in GL261 cells exposed to RCT promoted senescence and induced robust genomic instability, leading to mitotic death. (5) Coculture experiments of GL261-Ang2 cells with RAW 264.7 cells resulted in a significant increase in macrophage migration, which was abrogated by the addition of soluble Tie2 receptor. (6) Together, these preclinical results showed that, combined with RCT, Ang2 acted in an autocrine manner by increasing GB cell senescence and in a paracrine manner by acting on the innate immune system while modulating the vascular tumor compartment. On this preclinical model, we found that an ectopic expression of Ang2 combined with RCT impedes tumor recurrence.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15177-15177
Author(s):  
A. S. Kennedy ◽  
W. A. Dezarn ◽  
P. McNeillie ◽  
M. England ◽  
C. Overton ◽  
...  

15177 Background: Liver tolerance to reirradiation with multiple doses of 90Y-microspheres is not known. Many patients (pts) have also received external beam radiotherapy to the liver or through the liver and are surviving long enough to be considered for a second and third liver treatments with internal radiation. Methods: The experience of a single center treating liver tumors with resin 90Y-microspheres was used. Pts that received liver radiation prior to or after resin microsphere therapy were studied. Endpoints were toxicity, tumor response, disease type, latency period between radiation treatments, shunting to lung, and effects on liver volume and function. The delivery activity of microspheres selected was not reduced below that which was typically chosen for patients without prior liver radiation which was 25% reduced from the manufacturer’s BSA dose calculation method. All patients received bilobar microsphere delivery during a single session. Results: A total of 40 pts were identified; 14 women, 26 men, treated 6/2003 to 12/2006, with 35 pts receiving 2 courses and 5 pts with 3 courses of liver radiation. Retreatment with resin microspheres 26 pts, prior external beam radiation in 7 pts, prior glass microspheres in 2pts, prior systemic radiotherapy in 2 pts, and prior stereotactic liver radiation in 1 pt. Liver function was stable and adequate in all patients after additional liver radiation, and no pts developed radiation-induced liver dysfunction (RILD) or veno-occlusive disease (VOD). The percentage of shunting to the lung decreased with retreatment. Tumors treated: 14 carcinoid, 11 colorectal, 6 hepatocellular and cholangiocarcinoma, 2 sarcoma, 3 unknown primary, 1 each of breast, esophagus, and head and neck primaries. Conclusions: Repeated radiation to the liver with 90Y-microspheres appears safe in patients that have sufficient normal liver function and reserve based on known laboratory parameters already used for selection of microsphere therapy. No acute life-threatening, fatal, or late liver damage was observed, i.e. RILD or VOD. No specific dose reduction is recommended for retreatment of the liver. No significant financial relationships to disclose.


2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 218-218
Author(s):  
A. J. McRee ◽  
S. Chen ◽  
B. H. O'Neil ◽  
K. Rathmell

218 Background: Cholangiocarcinoma (CC) is an aggressive malignancy that often presents in advanced stages with poor response rates to conventional chemotherapy. Recent studies of CC have uncovered several oncogenes and tumor suppressors implicated in the transition from biliary hyperplasia to malignancy. We have developed a mouse model of intrahepatic CC that results from deletion of the phosphatase and tensin homolog (PTEN) gene and the von Hippel Lindau (VHL) gene, a tumor suppressor that regulates hypoxia inducible factor (HIF) expression. Immunohistochemical (IHC) analysis of the liver tumors revealed strong staining of p-AKT and HIF-1α. This study aims to determine the expression of the same downstream targets p-AKT and HIF1α in a dataset of human CC tumors. Methods: Archived samples from 33 CC patients were sectioned and stained via IHC for p-AKT and HIF1α expression. Samples were evaluated using a proportion score (PS) for neoplastic cells on a scale of 0 to 5, and an intensity score (IS) expressed on a scale of 0 to 3. Normal liver samples were used as controls. Results: Using a combined score of at least 5 to determine positive expression, 18% of the 33 evaluated samples displayed positive p-AKT expression and 61% displayed positive HIF1α expression. 15% of cases displayed concomitant expression of both p-AKT and HIF1α, while 39% of evaluated samples had expression of neither protein. Conclusions: Delineating the molecular pathways that lead to CC formation is crucial in developing novel therapeutics for a disease in drastic need of more effective therapies. Our group has developed a mouse model of intrahepatic CC that suggests a synergistic role of PTEN and VHL in the tumorigenesis of CC with upregulation of p-AKT and HIF1α. A modest percentage of a cohort of human samples demonstrates a similar expression pattern, potentially defining a distinct molecular subtype of this cancer with implications for tumor behavior and response to treatment. Future studies will correlate these molecularly-defined subtypes to the clinicopathologic characteristics of the tumors with the ultimate aim of establishing biomarkers of disease prognosis as well as potential predictive indicators of treatment activity. No significant financial relationships to disclose.


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