Perfusion and diffusion sensitive C stimulated-echo MRSI for metabolic imaging of cancer

Metabolic imaging with hyperpolarized [1-¹³C]-pyruvate can rapidly probe tissue metabolic profiles in vivo and has been shown to provide cancer imaging biomarkers for tumor detection, progression, and response to therapy. This technique uses a bolus injection followed by imaging within 1–2 minutes. The observed metabolites include vascular components and their generation is also influenced by cellular transport. These factors complicate image interpretation, especially since [1-¹³C]lactate, a metabolic product that is a biomarker of cancer, is also produced by red blood cells. It would be valuable to understand the distribution of metabolites between the vasculature, interstitial space, and intracellular compartments. The purpose of this study was to better understand this compartmentalization by using a perfusion and diffusion-sensitive stimulated-echo acquisition mode (STEAM) MRSI acquisition method tailored to hyperpolarized substrates. Our results in mouse models showed that among metabolites, the injected substrate ¹³C-pyruvate had the largest vascular fraction overall while ¹³C-alanine had the smallest vascular fraction. We observed a larger vascular fraction of pyruvate and lactate in the kidneys and liver when compared to back muscle and prostate tumor tissue. Our data suggests that ¹³C-lactate in prostate tumor tissue voxels was the most abundant labeled metabolite intracellularly. This was shown in STEAM images that highlighted abnormal cancer cell metabolism and suppressed vascular ¹³C metabolite signals.     

利用基于~1H NMR的代谢组学分析研究重离子辐射对大鼠额叶皮质区的影响

太空辐射尤其是重离子辐射可造成DNA的破坏、细胞死亡、以及一些癌症的发生,是人类深空探索进程中急需克服的难题. 本文通过重离子加速器产生¹²C⁶⁺重离子束对大鼠头部进行一定剂量的辐射,模拟空间重离子辐射对中枢神经系统(CNS)的生物学效应. 采用基于¹H NMR的代谢组学方法对辐射大鼠大脑额叶皮质区进行了测定分析,结合数据的统计分析和检验,发现了包括一些重要CNS神经递质在内的代谢物含量发生明显变化. 这些代谢物主要为：牛磺酸、乳酸、谷氨酸、4-氨基丁酸、以及磷酸胆碱等. 结合差异蛋白质组结果分析,包括4-氨基丁酸、谷氨酸、乳酸、牛磺酸等在内的代谢物参与的主要生物途径,如神经递质的合成途径,以及神经递质受体介导的信号途径可能受重离子辐射的负面影响. 这些发现将为进一步阐明重离子辐射效应的分子机制提供有利信息,从而为从生物学途径探寻有效重离子辐射防护措施提供依据.     

The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-C]-ketoisocaproate

Recent advancements in the field of hyperpolarized ¹³C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-¹³C]-2-ketoisocaproate ([1-¹³C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-¹³C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-¹³C]-KIC to the metabolic product, [1-¹³C]-leucine ([1-¹³C]-Leu), could be monitored via hyperpolarized ¹³C MRS.     

13C/12C-Untersuchungen an Tumorzellen

Abstract

The metabolism of tumor-cells differs in many ways from normal (healthy) cells. One of the major differences is the high glycolytic activity in tumor-cells with the subsequent formation of lactate from glucose, even in the presence of oxygen. The question whether this high rate of glycolysis has any effect on the ¹³C/¹²C-relation of the cells is examined in experiments with a tumor-cell line (HT29) and in specimens of human breast cancer.

The HT29 cells show a clear decrease in ¹³C content compared to their culture medium (Δδ = 3.28‰).

Tissue from human breast cancer has more ¹³C than normal breast tissue taken from the same patient ((Δδ = 2.74‰). But the content of fat is much higher in the normal tissue and its δ-value is negatively correlated with its fat content. It is concluded that the difference between normal and tumor tissue is due to the heterogeneous composition of the normal tissue samples.     

Frequency-specific SSFP for hyperpolarized C metabolic imaging at 14.1 T

Metabolic imaging of hyperpolarized [1-¹³C] pyruvate co-polarized with [¹³C]urea by dynamic nuclear polarization with rapid dissolution is a promising new method for assessing tumor metabolism and perfusion simultaneously in vivo. Novel pulse sequences are required to enable dynamic imaging of multiple ¹³C spectral lines with high spatiotemporal resolution. The goal of this study was to investigate a new frequency-specific approach for rapid metabolic imaging of multiple ¹³C resonances using the spectral selectivity of steady-state free precession pulse (SSFP) trains. Methods developed in simulations were implemented in a dynamic frequency-cycled balanced SSFP pulse sequence on a 14.1-T animal magnetic resonance imaging scanner. This acquisition was tested in thermal and hyperpolarized phantom imaging studies and in a transgenic mouse with prostate cancer.     

Analysis of hyperpolarized dynamic C lactate imaging in a transgenic mouse model of prostate cancer

This study investigated the application of an acquisition that selectively excites the [1-¹³C]lactate resonance and allows dynamic tracking of the conversion of ¹³C-lactate from hyperpolarized ¹³C-pyruvate at a high spatial resolution. In order to characterize metabolic processes occurring in a mouse model of prostate cancer, 20 sequential 3D images of ¹³C-lactate were acquired 5 s apart using a pulse sequence that incorporated a spectral–spatial excitation pulse and a flyback echo-planar readout to track the time course of newly converted ¹³C-lactate after injection of prepolarized ¹³C-pyruvate. The maximum lactate signal (MLS), full-width half-maximum (FWHM), time to the peak ¹³C-lactate signal (TTP) and area under the dynamic curve were calculated from the dynamic images of 10 TRAMP mice and two wild-type controls. The regional variation in ¹³C-lactate associated with the injected pyruvate was demonstrated by the peak of the ¹³C-lactate signal occurring earlier in the kidney than in the tumor region. The intensity of the dynamic ¹³C-lactate curves also varied spatially within the tumor, illustrating the heterogeneity in metabolism that was most prominent in more advanced stages of disease development. The MLS was significantly higher in TRAMP mice that had advanced disease.     

Measuring the link between cardiac mechanical function and metabolism during hyperpolarized 13C-pyruvate magnetic resonance experiments

PurposeThe goal of this study was to develop a methodology to investigate the relationship between contractile function and hyperpolarized (HP) [1-¹³C]pyruvate metabolism in a small animal model. To achieve sufficient signal from HP ¹³C compounds, HP ¹³C MRS/MRSI has required relatively large infusion volumes relative to the total blood volume in small animal models, which may affect cardiac function.MethodsEight female Sprague Dawley rats were imaged on a 4.7T scanner with a dual tuned ¹H/¹³C volume coil. ECG and respiratory gated k-t spiral MRSI and an IDEAL based reconstruction to determine [1-¹³C]pyruvate metabolism in the myocardium. This was coupled with ¹H cine MRI to determine ventricular volumes and mechanical function pre- and post-infusion of [1-¹³C]pyruvate. For comparison to the [1-¹³C]pyruvate experiments, three female Sprague Dawley rats were imaged with ¹H cine MRI to determine myocardial function pre- and post-saline infusion.ResultsWe demonstrated significant changes in cardiac contractile function between pre- and post-infusion of [1-¹³C]pyruvate. Specifically, there was an increase in end-diastolic volume (EDV), stroke volume (SV), and ejection fraction (EF). Additionally, the ventricular vascular coupling ratio (VVCR) showed an improvement after [1-¹³C]pyruvate infusion, indicating increased systolic performance due to an increased arterial load. There was a moderate to strong relationship between the downstream metabolic conversion of pyruvate to bicarbonate and a strong relationship between the conversion of pyruvate to lactate and the cardiac mechanical function response.ConclusionThe infusion of [1-¹³C]pyruvate resulted in demonstrable increases in contractile function which was related to pyruvate conversion to bicarbonate and lactate. The combined effects of the infusion volume and inotropic effects of pyruvate metabolism likely explains the augmentation in myocardial mechanical function seen in these experiments. Given the relationship between pyruvate metabolism and contractile function observed in this study, this methodological approach may be utilized to better understand cardiac metabolic and functional remodeling in heart disease.     

In vivo C magnetic resonance spectroscopy of a human brain tumor after application of C-1-enriched glucose

Objectives

As a unique tool to assess metabolic fluxes noninvasively, ¹³C magnetic resonance spectroscopy (MRS) could help to characterize and understand malignancy in human tumors. However, its low sensitivity has hampered applications in patients. The aim of this study was to demonstrate that with sensitivity-optimized localized ¹³C MRS and intravenous infusion of [1-¹³C]glucose under euglycemia, it is possible to assess the dynamic conversion of glucose into its metabolic products in vivo in human glioma tissue.

Materials and Methods

Measurements were done at 3 T with a broadband single RF channel and a quadrature ¹³C surface coil inserted in a ¹H volume coil. A ¹H/¹³C polarization transfer sequence was applied, modified for localized acquisition, alternatively in two (50 ml) voxels, one encompassing the tumor and the other normal brain tissue.

Results

After about 20 min of [1-¹³C]glucose infusion, a [3-¹³C]lactate signal appeared among several resonances of metabolic products of glucose in MR spectra of the tumor voxel. The resonance of [3-¹³C]lactate was absent in MR spectra from contralateral tissue. In addition, the intensity of [1-¹³C]glucose signals in the tumor area was about 50% higher than that in normal tissue, likely reflecting more glucose in extracellular space due to a defective blood–brain barrier. The signal intensity for metabolites produced in or via the tricarboxylic acid (TCA) cycle was lower in the tumor than in the contralateral area, albeit that the ratios of isotopomer signals were comparable.

Conclusion

With an improved ¹³C MRS approach, the uptake of glucose and its conversion into metabolites such as lactate can be monitored noninvasively in vivo in human brain tumors. This opens the way to assessing metabolic activity in human tumor tissue.     

Gd-DTPA-induced dynamic metabonomic changes in rat biofluids

ObjectivesThe purposes of this study were (1) to detect the dynamic metabonomic changes induced by gadopentetate dimeglumine (Gd-DTPA) and (2) to investigate the potential metabolic disturbances associated with the pathogenesis of nephrogenic systemic fibrosis (NSF) at the early stage.MethodsA nuclear magnetic resonance (NMR)-based metabolomics approach was used to investigate the urinary and serum metabolic changes induced by a single tail vein injection of Gd-DTPA (dosed at 2 and 5 mmol/kg body weight) in rats. Urine and serum samples were collected on days 1, 2 and 7 after dosing.ResultsMetabolic responses of rats to Gd-DTPA administration were systematic involving changes in lipid metabolism, glucose metabolism, TCA cycle, amino acid metabolism and gut microbiota functions. Urinary and serum metabonomic recovery could be observed in both the 2 and 5 mmol/kg body weight group, but the metabolic effects of high-dosed (5 mmol/kg body weight) Gd-DTPA lasted longer. It is worth noting that hyperlipidemia was observed after Gd-DTPA injection, and nicotinate might play a role in the subsequent self-recovery of lipid metabolism. The disturbance of tyrosine, glutamate and gut microbiota metabolism might associate with the progression of NSF.ConclusionThese findings offered essential information about the metabolic changes induced by Gd-DTPA, and could be potentially important for investigating the pathogenesis of NSF at the early stage. Moreover, the recovery of rats administrated with Gd-DTPA may have implications in the treatment of early stage NSF.     

Rapid sequential injections of hyperpolarized [1-C]pyruvate in vivo using a sub-kelvin,multi-sample DNP polarizer

The development of hyperpolarized technology utilizing dynamic nuclear polarization (DNP) has enabled the rapid measurement of ¹³C metabolism in vivo with very high SNR. However, with traditional DNP equipment, consecutive injections of a hyperpolarized compound in an animal have been subject to a practical minimum time between injections governed by the polarization build-up time, which is on the order of an hour for [1-¹³C]pyruvate. This has precluded the monitoring of metabolic changes occurring on a faster time scale. In this study, we demonstrated the ability to acquire in vivo dynamic magnetic resonance spectroscopy (MRS) and 3D magnetic resonance spectroscopic imaging (MRSI) data in normal rats with a 5 min interval between injections of hyperpolarized [1-¹³C]pyruvate using a prototype, sub-Kelvin dynamic nuclear polarizer with the capability to simultaneously polarize up to 4 samples and dissolve them in rapid succession. There were minimal perturbations in the hyperpolarized spectra as a result of the multiple injections, suggesting that such an approach would not confound the investigation of metabolism occurring on this time scale. As an initial demonstration of the application of this technology and approach for monitoring rapid changes in metabolism as a result of a physiological intervention, we investigated the pharmacodynamics of the anti-cancer agent dichloroacetate (DCA), collecting hyperpolarized data before administration of DCA, 1 min after administration, and 6 min after administration. Dramatic increases in ¹³C-bicarbonate were detected just 1 min (as well as 6 min) after DCA administration.     

In situ 19F MRS measurement of RIF-1 tumor blood volume: Corroboration by radioisotope-labeled [125I]-albumin and correlation to tumor size

Tumor blood volume (TBV) is an important factor in the metabolism of a tumor and in its response to therapy. Until recently, the only methods to determine TBV were highly invasive and many involved radioisotopes. In this study, a perfluorocarbon (PFC) emulsion, Oxypherol, was monitored by ¹⁹F magnetic resonance spectroscopy (MRS). TBVs, as determined by ¹⁹F MRS of in situ and excised radiation-induced fibrosarcoma (RIF-1) tumors (n = 9), were strongly correlated with the TBV measured by a radioisotope labeled albumin method (slopes of 1.1 and 0.8 with R = 0.86 and 0.91, respectively, by linear regression). In general, the TBV as calculated from the in situ MRS measurements (n = 24) decreased from 28 to 5 ml/100 g tumor mass for tumors ranging in mass from 0.15 to 2 g. However, there was an indication of an initial increase of TBV in tumors smaller than 0.5 g.     

Kinetic modeling of hyperpolarized 13C1-pyruvate metabolism in normal rats and TRAMP mice

PurposeTo investigate metabolic exchange between ¹³C₁-pyruvate, ¹³C₁-lactate, and ¹³C₁-alanine in pre-clinical model systems using kinetic modeling of dynamic hyperpolarized ¹³C spectroscopic data and to examine the relationship between fitted parameters and dose–response.Materials and methodsDynamic ¹³C spectroscopy data were acquired in normal rats, wild type mice, and mice with transgenic prostate tumors (TRAMP) either within a single slice or using a one-dimensional echo-planar spectroscopic imaging (1D-EPSI) encoding technique. Rate constants were estimated by fitting a set of exponential equations to the dynamic data. Variations in fitted parameters were used to determine model robustness in 15 mm slices centered on normal rat kidneys. Parameter values were used to investigate differences in metabolism between and within TRAMP and wild type mice.ResultsThe kinetic model was shown here to be robust when fitting data from a rat given similar doses. In normal rats, Michaelis–Menten kinetics were able to describe the dose–response of the fitted exchange rate constants with a 13.65% and 16.75% scaled fitting error (SFE) for k_pyr→lac and k_pyr→ala, respectively. In TRAMP mice, k_pyr→lac increased an average of 94% after up to 23 days of disease progression, whether the mice were untreated or treated with casodex. Parameters estimated from dynamic ¹³C 1D-EPSI data were able to differentiate anatomical structures within both wild type and TRAMP mice.ConclusionsThe metabolic parameters estimated using this approach may be useful for in vivo monitoring of tumor progression and treatment efficacy, as well as to distinguish between various tissues based on metabolic activity.     

Poly(ADP-ribose) polymerase-1 gene in human tumor cell lines: Its expression and structural alteration

Poly(ADP-ribose) polymerase-1 (Parp-1) is involved in DNA repair and cell-death induction after DNA damage. Parp-1^−/− mice show higher susceptibility to the carcinogenic effects of nitrosamine and azoxymethane. To elucidate the role of alterations of the PARP-1 gene in human carcinogenesis, we examined the expression level of PARP-1 gene in various human tumor cell lines. The presence of gross rearrangement of PARP-1 gene in these cell lines was also examined by Southern blot hybridization analysis. The expression levels of PARP-1 gene in several cell lines, including T-cell leukemia cell lines (Molt-4 and CCRF-CEM), colon cancer cell line (WiDr), and gastric cancer cell lines (KATOIII, OKAJIMA, and MKN45) was substantially lower than in other cancer cell lines. Among the 85 analyzed cell lines, structural alteration of PARP-1 gene was detected in a gastric cancer cell line, MKN28. A low level of PARP-1 expression in human cancer could potentially influence cancer cell growth, differentiation and cancer development by affecting genomic instability, as well as the response of tumors to chemo- and radiotherapy.     

Relaxometric investigations addressing the determination of intracellular water lifetime: a novel tumour biomarker of general applicability

ABSTRACT

¹H Fast-Field Cycling NMR relaxometry is proposed as a powerful method to investigate tumour cell metabolism by measuring changes in cell water content and mobility across the cellular membrane. Measurements of intracellular water residence time in cultured cells were carried out by measuring T₁ at fixed field (0.2?T) after the addition of a paramagnetic Gd complex (Prohance) at different concentrations in the external medium. Investigations on tumour cells (mammary adenocarcinoma TS/A) grown in normo- or hypoxic conditions or suspended in ‘hypo-osmotic’ solutions allowed us to demonstrate that both hypoxic and hypo-osmotic conditions cause a marked increase in water mobility as assessed by the elongation of T₁. Conversely, the metabolic change caused by glutamine (an aminoacid essential for tumour growth) deprivation caused a water mobility decrease (shorter T₁). These findings suggest that T₁ measurements at low and variable magnetic field strengths, giving access to the assessment of intracellular water lifetime, can provide important information about tumour cell metabolism in real time and non-invasively.     

Synchronized 13C-15N-NMR Spectroscopy to Follow Kinetics of Glycine Metabolization in the Rat Liver Non-Destructively

A method is proposed for reiterated measurements by turns of ¹³C and ¹⁵N NMR signals at intact rat liver tissue. Eight minutes after Wistar rats had been injected 1,2-¹³C; ¹⁵Nglycine, the liver was excised and stored in the triple resonance probe-head of a 2.1 Tesla NMR spectrometer. Alternatively ¹³C and ¹⁵N spectra were taken over some hours. Continued enzymatic activities of the liver tissue were seen in terms of metabolic changes of each of the carbon and nitrogen groups of glycine. Different half lives were found for the disappearance of the groups. The measurements gave insights into the kinetics and metabolism of an amino acid as an example to follow the vitality of an isolated organ non-destructively.     

Analysis of metabolic pools in broilers chicks

This paper shows the possibility of obtaining new parameters for the mathematical modelling of data on stable isotopes in biological systems and its application in obtaining data on metabolic pools of blood plasma, blood serum, liver and muscle of broilers. This theory states that the modelling of turnover used for studies of isotopic incorporation when the metabolism has a single metabolic pool is feasible by the technique of setting an exponential. However, when the metabolism has more than one metabolic pool, it is necessary to apply the linearization technique, linear regression adjustment and evaluation of the assumptions of regression to obtain the kinetic parameters such as half-life (T_1/2) and isotope exchange rate (k). The application of this technique on carbon-13 data from 100 one-day-old chicks, with the change of diet composed of grains of the photosynthetic cycle of plants from C₄ to C₃, in broilers has enabled the discovery that the liver, blood plasma and blood serum have a single metabolic pool; however, the pectoral muscle has two metabolic pools. For the liver, blood plasma and blood serum, the half-life values were found by the exponential fit being T_1/2?=?1.4 days with the rate of exchange of k?=?0.502, T_1/2?=?2.4 days with k?=?0.293 and T_1/2?=?2.0 days with k?=?0.348, respectively. For the pectoral muscle, after linearization, the half-life values were found for T_1/2(1)?=?1.7 and T_1/2(2)?=?3 days, with exchange rates of k₁?=?0.405 and k₂?=?0.235, representing approximately 66 and 34?%, respectively.     

Mapping phosphorylation rate of fluoro-deoxy-glucose in rat brain by F chemical shift imaging

¹⁹F magnetic resonance spectroscopy (MRS) studies of 2-fluoro-2-deoxy-d-glucose (FDG) and 2-fluoro-2-deoxy-d-glucose-6-phosphate (FDG-6P) can be used for directly assessing total glucose metabolism in vivo. To date, ¹⁹F MRS measurements of FDG phosphorylation in the brain have either been achieved ex vivo from extracted tissue or in vivo by unusually long acquisition times. Electrophysiological and functional magnetic resonance imaging (fMRI) measurements indicate that FDG doses up to 500 mg/kg can be tolerated with minimal side effects on cerebral physiology and evoked fMRI-BOLD responses to forepaw stimulation. In halothane-anesthetized rats, we report localized in vivo detection and separation of FDG and FDG-6P MRS signals with ¹⁹F 2D chemical shift imaging (CSI) at 11.7 T. A metabolic model based on reversible transport between plasma and brain tissue, which included a non-saturable plasma to tissue component, was used to calculate spatial distribution of FDG and FDG-6P concentrations in rat brain. In addition, spatial distribution of rate constants and metabolic fluxes of FDG to FDG-6P conversion were estimated. Mapping the rate of FDG to FDG-6P conversion by ¹⁹F CSI provides an MR methodology that could impact other in vivo applications such as characterization of tumor pathophysiology.     

SIRT7基因低表达胶质瘤细胞株代谢特征的NMR分析

肿瘤是一种代谢疾病，癌基因表达对肿瘤细胞代谢的影响是目前肿瘤研究的热点之一.本文利用基于核磁共振氢谱（¹H NMR）的代谢组学方法对癌基因SIRT7低表达胶质瘤细胞株的代谢特征进行分析，寻找与SIRT7基因表达相关的特征性代谢物和代谢通路.分析结果表明，SIRT7基因低表达组与对照组细胞的代谢轮廓存在显著性差异，其细胞水溶性萃取物中有22种代谢物浓度发生明显变化.与对照组相比，SIRT7基因低表达胶质瘤细胞株中乳酸、甘氨酸、谷氨酸等12种代谢物浓度升高；缬氨酸、亮氨酸、赖氨酸等10种代谢物浓度降低.通路富集分析提示氨酰-tRNA生物合成、氨基酸代谢等代谢通路与SIRT7低表达密切相关.以上结果为进一步阐明癌基因SIRT7调控胶质瘤细胞代谢的作用机制提供了理论依据.     

Design of spectral-spatial outer volume suppression RF pulses for tissue specific metabolic characterization with hyperpolarized C pyruvate

[1-¹³C] pyruvate pre-polarized via DNP has been used in animal models to probe changes in metabolic enzyme activities in vivo. To more accurately assess the metabolic state and its change from disease progression or therapy in a specific region or tissue in vivo, it may be desirable to separate the downstream ¹³C metabolite signals resulting from the metabolic activity within the tissue of interest and those brought into the tissue by perfusion. In this study, a spectral-spatial saturation pulse that selectively saturates the signal from the metabolic products [1-¹³C] lactate and [1-¹³C] alanine was designed and implemented as outer volume suppression for localized MRSI acquisition. Preliminary in vivo results showed that the suppression pulse did not prevent the pre-polarized pyruvate from being delivered throughout the animal while it saturated the metabolites within the targeted saturation region.     

Dynamic contrast-enhanced MRI of gastric cancer: Correlations of the pharmacokinetic parameters with histological type,Lauren classification,and angiogenesis

PurposeTo compare the pharmacokinetic parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in gastric cancers of different histological type and Lauren classification, and to investigate whether DCE-MRI parameters correlate with vascular endothelial growth factor (VEGF) expression levels in gastric cancer.MethodsIncluded were 32 patients with gastric cancer who underwent DCE-MRI of the upper abdomen before tumor resection. DCE-MRI parameters including the volume transfer coefficient (K^trans), reverse reflux rate constant (K_ep), and extracellular extravascular volume fraction (V_e) were calculated from the tumor region. Post-operative specimens were used for determination of histological differentiation (i.e., non-mucinous, mucinous, or signet-ring-cell adenocarcinoma) as well as Lauren classification (intestinal type or diffuse type). VEGF expression was examined for assessing angiogenesis. DCE-MRI parameters with different histological type and Lauren classification were compared using independent samples t-test and analysis of variance, respectively. Correlations between DCE-MRI parameters and VEGF expression grades were tested using Spearman correlation analysis.ResultsAmong gastric adenocarcinomas of three different histological types, mucinous adenocarcinomas showed a higher V_e and lower K^trans than the others (P < 0.01). Between the two Lauren classifications, the diffuse type showed a higher V_e than the intestinal type (P < 0.001). The mean K^trans showed a significantly positive correlation with VEGF (r = 0.762, P < 0.001).ConclusionDCE-MRI permits noninvasive prediction of tumor histological type and Lauren classification and estimation of tumor angiogenesis in gastric cancer. DCE-MRI parameters can be used as imaging biomarkers to predict the biologic aggressiveness of a tumor as well as patient prognosis.