Kinetic and perfusion modeling of hyperpolarized (13)C pyruvate and urea in cancer with arbitrary RF flip angles

Quantitative imaging in medicine and surgery 02/2014; 4(1):24-32. DOI: 10.3978/j.issn.2223-4292.2014.02.02
Source: PubMed


The accurate detection and characterization of cancerous tissue is still a major problem for the clinical management of individual cancer patients and for monitoring their response to therapy. MRI with hyperpolarized agents is a promising technique for cancer characterization because it can non-invasively provide a local assessment of the tissue metabolic profile. In this work, we measured the kinetics of hyperpolarized [1-(13)C] pyruvate and (13)C-urea in prostate and liver tumor models using a compressed sensing dynamic MRSI method. A kinetic model fitting method was developed that incorporated arbitrary RF flip angle excitation and measured a pyruvate to lactate conversion rate, Kpl, of 0.050 and 0.052 (1/s) in prostate and liver tumors, respectively, which was significantly higher than Kpl in healthy tissues [Kpl =0.028 (1/s), P<0.001]. Kpl was highly correlated to the total lactate to total pyruvate signal ratio (correlation coefficient =0.95). We additionally characterized the total pyruvate and urea perfusion, as in cancerous tissue there is both existing vasculature and neovascularization as different kinds of lesions surpass the normal blood supply, including small circulation disturbance in some of the abnormal vessels. A significantly higher perfusion of pyruvate (accounting for conversion to lactate and alanine) relative to urea perfusion was seen in cancerous tissues (liver cancer and prostate cancer) compared to healthy tissues (P<0.001), presumably due to high pyruvate uptake in tumors.

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    ABSTRACT: The accurate detection and characterization of cancerous tissue is still a major problem for the clinical management of individual prostate cancer patients and for monitoring their response to therapy. ρ1 (TR times to times points per second over T1 ratio) of urea, pyruvate, lactate, and alanine, also the amount urea and pyruvate perfusion, and conversion constant between pyruvate to lactate(Kpl) and pyruvate to alanine(Kpa) are important parameters in different organs including cancerous and healthy tissues. ρ 1 of urea in kidneys, prostate cancerous tissues, and liver are measured 0.13(1/s), 0.15(1/s), and 0.075(1/s), respectively and ρ 1 of pyruvate in kidneys, liver cancer and healthy part of liver is 0.08(1/s), 0.13(1/s), and 0.064(1/s), respectively with TR=250ms. Kpl in cancerous tissues are more than 0.44(1/s) which is significantly higher than Kpl of metabolites in healthy tissues (Kpl = 0.028(1/s)) with p value less than 0.001. This Kpl is proportional to the lactate signal to pyruvate signal ratio with Correlation Coefficient=0.95. High perfusion amount of the accumulation of pyruvate, lactate, and alanine in compare to urea perfusion has been seen in cancerous tissues (liver cancer and prostate cancer) significantly (p<0.001) less than in healthy tissues.
    Full-text · Thesis · Aug 2013

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    ABSTRACT: Transarterial chemoembolization (TACE) is a form of intra-arterial catheter-based chemotherapy that selectively delivers high doses of cytotoxic drug to the tumor bed combining with the effect of ischemic necrosis induced by arterial embolization. Chemoembolization and radioembolization are at the core of the treatment of liver hepatocellular carcinoma (HCC) patients who cannot receive potentially curative therapies such as transplantation, resection or percutaneous ablation. TACE for liver cancer has been proven to be useful in local tumor control, to prevent tumor progression, prolong patients' life and control patient symptoms. Recent evidence showed in patients with single-nodule HCC of 3 cm or smaller without vascular invasion, the 5-year overall survival (OS) with TACE was similar to that with hepatic resection and radiofrequency ablation. Although being used for decades, Lipiodol(®) (Lipiodol(®) Ultra Fluid(®), Guerbet, France) remains important as a tumor-seeking and radio-opaque drug delivery vector in interventional oncology. There have been efforts to improve the delivery of chemotherapeutic agents to tumors. Drug-eluting bead (DEB) is a relatively novel drug delivery embolization system which allows for fixed dosing and the ability to release the anticancer agents in a sustained manner. Three DEBs are available, i.e., Tandem(®) (CeloNova Biosciences Inc., USA), DC-Beads(®) (BTG, UK) and HepaSphere(®) (BioSphere Medical, Inc., USA). Transarterial radioembolization (TARE) technique has been developed, and proven to be efficient and safe in advanced liver cancers and those with vascular complications. Two types of radioembolization microspheres are available i.e., SIR-Spheres(®) (Sirtex Medical Limited, Australia) and TheraSphere(®) (BTG, UK). This review describes the basic procedure of TACE, properties and efficacy of some chemoembolization systems and radioembolization agents which are commercially available and/or currently under clinical evaluation. The key clinical trials of transcatheter arterial therapy for liver cancer are summarized.
    Full-text · Article · Apr 2015 · Chinese Journal of Cancer Research
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