The C-neu mammary carcinoma in Oncomice; characterization and monitoring response to treatment with herceptin by magnetic resonance methods

To characterize spontaneously occurring c-neu/HER2 overexpressing tumours in oncomice and their response to herceptin by non-invasive magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI). Oncomice were monitored by localized ³¹P MRS during unperturbed growth and before and after treatment with 10 mg/kg herceptin (Hoffman La Roche) intraperitoneally for up to 21 days post-treatment. Vascular morphology and function was assessed by quantitation of tumour magnetic resonance (MR) relaxation rates R₂* and R₂ prior to and either during carbogen (95% O₂/5% CO₂) breathing or following administration of the blood-pool contrast agent NC100150 (Clariscan, Amersham Health). Immunohistochemistry showed strong membrane staining for HER2 protein overexpression. The ³¹P MRS showed only a significant (p<0.01) increase of phosphomonoester / total phosphate ratio over 21 days of growth. Herceptin increased the tumour volume doubling time compared to untreated tumours and significantly increased the phosphomonoester / -nucleoside triphosphate ratio 2 days after treatment (p=0.01). Tumours showed a highly heterogeneous yet significant (p<0.01) decrease or increase in R₂* in response to carbogen or NC100150 respectively. The absence of a decline in tumour bioenergetics with growth, commonly seen in ³¹P MRS studies of transplanted rodent tumour models, coupled with the heterogeneous blood volume revealed by ¹H MRI, suggest a metabolic and vascular phenotype similar to that found in human tumours.     

Comparison of plasma and peritoneal concentrations of various categories of MRI blood pool agents in a murine experimental pharmacokinetic model

The aim of this study was to validate an experimental model designed to distinguish four categories of contrast agents, non specific agents (NDA, Gd-DOTA) characterized by rapid and total extravasation; low diffusion agents (LDA, P760) characterized by delayed extravasation; and rapid (P792) and slow clearance (P717) blood pool agents (BPA) characterized by limited extravasation. Plasma and peritoneal gadolinium concentrations were simultaneously measured after intravenous injection of various contrast agents in mice. Products of each category were compared in this model. The plasma pharmacokinetic profiles were similar for Gd-DOTA and P760 (t1/2 = 13.3 and 13.8 min. respectively), whereas the half-lives were 22 and 1212 min for P792 and P717, respectively. The plasma clearance was inversely related to the size of the contrast agent. The intraperitoneal diffusion patterns of the various products were related to the molecular volume; C_max per dose decreased progressively (78.7, 51.2, 44.2, 33.5 1/1) and t_max increased (7, 15, 40, and 120 min) for Gd-DOTA, P760, P792 and P717, respectively. Nevertheless, the same quantities of Gd-DOTA and P760 (AUC ratio of 78.4 and 76.8, respectively) diffused into the peritoneum, whereas only 44.5% of P792 and 21.5% of P717 extravasated. The data obtained in this peritoneal permeability model with the various categories of contrast agents provide an estimation of the quantities of contrast agents diffusing into a permeable interstitium and may be used to predict the corresponding signal intensity, which can be measured locally.     

Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas

The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF- and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)₄₅. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K^PS) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K^PS and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K^PS post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.     

MRI-based assessment of liver perfusion and hepatocyte injury in the murine model of acute hepatitis

Objective

To assess alterations in perfusion and liver function in the concanavalin A (ConA)-induced mouse model of acute liver failure (ALF) using two magnetic resonance imaging (MRI)-based methods: dynamic contrast-enhanced MRI (DCE-MRI) with Gd-EOB-DTPA contrast agent and arterial spin labelling (ASL).

Materials and methods

BALB/c mice were studied using a 9.4 T MRI system. The IntraGateFLASH^TM and FAIR-EPI pulse sequences were used for optimum mouse abdomen imaging.

Results

The average perfusion values for the liver of the control and ConA group were equal to 245 ± 20 and 200 ± 32 ml/min/100 g (p = 0.008, respectively). DCE-MRI showed that the time to the peak of the image enhancement was 6.14 ± 1.07 min and 9.72 ± 1.69 min in the control and ConA group (p < 0.001, respectively), while the rate of the contrast wash-out in the control and ConA group was 0.037 ± 0.008 and 0.021 ± 0.008 min^?1 (p = 0.004, respectively). These results were consistent with hepatocyte injury in the ConA-treated mice as confirmed by histopathological staining.

Conclusions

Both the ASL and DCE-MRI techniques represent a reliable methodology to assess alterations in liver perfusion and hepatocyte integrity in murine hepatitis.

     

Assessment of neovascular permeability in a pancreatic tumor model using dynamic contrast-enhanced (DCE) MRI with contrast agents of different molecular weights

Object  

We evaluated the relationship of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters and contrast agents with different molecular weights (MW) in a pancreatic tumor mouse model.     

Standardized MR protocol for the evaluation of MRA sequences and/or contrast agents effects in high-degree arterial stenosis analysis

Purpose To investigate the relative role of high resolution (spatial or temporal) magnetic resonance angiography (MRA) sequence and of contrast agent properties in the evaluation of high-degree arterial stenosis. Methods We qualitatively and quantitatively studied both 50 and 95% (300 μm diameter) stenosis of a 6 mm arterial phantom with two contrast agents (CA), Gd-DOTA (r₁ =2.9 mM⁻¹ s⁻¹) versus P760 (r₁ =25 mM⁻¹ s⁻¹) at several CA concentrations, including arterial peak concentration after injection of either a single or double dose of CA, using either a high temporal (booster) or high spatial (HR) resolution 3D MRA sequences. Experimental data were then compared to theoretical data. Results With the 3D HR sequence, both visual and quantitative analysis were significantly better compared to the 3D booster sequence, at each phantom diameter. Quantitative analysis was significantly improved by injection of a double versus a single dose of each CA (Gd-DOTA or P760), primarily in high degree stenosis. Conclusion Combined MRA spatial resolution and high CA efficiency are mandatory to correctly evaluate high degree stenosis.     

Non-contrast myocardial perfusion in rest and exercise stress using systolic flow-sensitive alternating inversion recovery

Objective

To evaluate systolic flow-sensitive alternating inversion recovery (FAIR) during rest and exercise stress using 2RR (two cardiac cycles) or 1RR intervals between inversion pulse and imaging.

Materials and methods

1RR and 2RR FAIR was implemented on a 3T scanner. Ten healthy subjects were scanned during rest and stress. Stress was performed using an in-bore ergometer. Heart rate, mean myocardial blood flow (MBF) and temporal signal-to-noise ratio (TSNR) were compared using paired t tests.

Results

Mean heart rate during stress was higher than rest for 1RR FAIR (85.8 ± 13.7 bpm vs 63.3 ± 11.1 bpm; p < 0.01) and 2RR FAIR (83.8 ± 14.2 bpm vs 63.1 ± 10.6 bpm; p < 0.01). Mean stress MBF was higher than rest for 1RR FAIR (2.97 ± 0.76 ml/g/min vs 1.43 ± 0.6 ml/g/min; p < 0.01) and 2RR FAIR (2.8 ± 0.96 ml/g/min vs 1.22 ± 0.59 ml/g/min; p < 0.01). Resting mean MBF was higher for 1RR FAIR than 2RR FAIR (p < 0.05), but not during stress. TSNR was lower for stress compared to rest for 1RR FAIR (4.52 ± 2.54 vs 10.12 ± 3.69; p < 0.01) and 2RR FAIR (7.36 ± 3.78 vs 12.41 ± 5.12; p < 0.01). 2RR FAIR TSNR was higher than 1RR FAIR for rest (p < 0.05) and stress (p < 0.001).

Discussion

We have demonstrated feasibility of systolic FAIR in rest and exercise stress. 2RR delay systolic FAIR enables non-contrast perfusion assessment during stress with relatively high TSNR.

     

Tumor microvasculature observed using different contrast agents: a comparison between Gd-DTPA-Albumin and B-22956/1 in an experimental model of mammary carcinoma

OBJECTIVE: The aim of this study was to compare a pure macromolecular contrast agent (Gd-DTPA-albumin) with a new protein-binding blood pool contrast agent (B22956/1) in terms of their capacity to investigate the microvasculature in an experimental model of mammary carcinoma. MATERIALS AND METHODS: Tumors were induced by subcutaneous injection of 5 x 10(5) BB1 cells into the backs of 5-7 week-old female FVB/neuNT233 mice. The animals were observed using DCE-MRI when the longest diameter of the tumor was 10.2+/-2.0 mm. DCE-MRI experiments were carried out using B22956/1 and (24 h later) Gd-DTPA-albumin. RESULTS: DCE-MRI data showed that vasculature in the tumor rim was characterized by greater fractional plasma volume and transendothelial permeability than vasculature in the tumor core as measured by both contrast agents. Permeability to Gd-DTPA-albumin in the tumor core was hardly measurable while permeability to B22956/1 was substantial. Histologically the tumor core showed areas of well vascularized, viable tissue surrounded by necrotic regions. CONCLUSIONS: DCE-MRI experiments performed with B22956/1 are useful in the investigation of vasculature in those tumor regions that are characterized by low permeability to macromolecules.     

Control of SF6 discharge gap switch by XeCl excimer laser

Experimental studies have been carried out on triggering characteristics of the SF₆ discharge gap switch by use of XeCl excimer laser (wavelength = 308 nm). First, laser irradiation characteristics are studied on a pure SF₆ in the pressure range of p = 160 ～ 3,800 torr. Using a lens of f (focal length) = 133 mm, the laser is irradiated into the gas, where the energy absorption is studied. If the laser is injected into the gas with the energy above a certain threshold for the breakdown, the rate of energy absorption is found to be ～ 17 percent of the incident energy at p > 760 torr. Injecting the laser into the SF₆-filled gap switch (gap length = 7 mm, p = 760 torr), we have studied the triggering characteristics. Excellent triggering characteristics were obtained; delay time for the discharge ～ 20 ns, and the jitter ～ 260 ps when the gap voltage is operated at 99 percent of the self-breakdown voltage. In addition, the triggering characteristics are studied by changing the focusing point axially. It is found that both the delay time and the jitter decrease when the focusing point tends to approach the high-voltage electrodes.     

Young Investigator Award Presentation at the 13th Annual Meeting of the ESMRMB, September 1996, Prague Quantification of pulmonary water compartments by magnetic resonance

The purpose of this study was to quantify pulmonary water compartments of total, intravascular, and extravascular lung water in excised and perfused sheep lungs with the use of magnetic resonance imaging techniques. Total lung water was measured by proton density maps calculated from multi-spin-echo images. Intravascular lung water was evaluated by magnetic resonance angiography before and after injection of gadolinium diethylenetriamine penta-acetic acid polylysine, a macromolecular paramagnetic contrast agent. Intravascular lung water was calculated from signal intensity histogram changes comparing pre- and postcontrast angiograms. Extravascular water was calculated as the difference between total and intravascular lung water. Quantities of total and intravascular lung water measured by magnetic resonance techniques were compared to reference results obtained from wet/dry weight gravimetry and Evans blue dilution performed after imaging. Magnetic resonance and reference results correlated significantly (total lung water:r=0.93,p<0.001; intravascular lung water:r=0.80,p<0.001; extravascular lung water:r=0.89,p<0.001). Therefore, we conclude that quantitative magnetic resonance techniques are potentially useful for the clinical evaluation of pulmonary water compartments.     

Use of spin-traps during warm ischemia-reperfusion in rat liver: comparative effect on energetic metabolism studied using31P nuclear magnetic resonance

Detection of free radicals by electron spin resonance (ESR) proves the involvement of reactive oxygen species (ROS) in reperfused organ injuries. Spin-traps are known to ameliorate hemodynamic parameters in an isolated postischemic heart. The effects of 5 mmol/L DMPO (5,5-dimethyl-1-pyrroline-N-oxide) or DEPMPO (5-(diethylphosphoryl)-5-methyl-1-pyrrolineN-oxide) on intracellular pH (pH_in) and ATP level were evaluated by³¹P nuclear magnetic resonance on isolated rat liver submitted to 1 hour of warm ischemia and reperfusion. At the end of the reperfusion period, during which pH_in recovered to its initial value (7.16±0.03) in all groups, the ATP recovery level (expressed in percentage of initial value) was similar in controls and DEPMPO (60%±5%,n=6 and 54%±4%,n=6, respectively), but only 37%±1% in DMPO-treated livers (n=6) (p<0.05 versus controls andp<0.05 versus DEPMPO). Oxidative phosphorylation was not affected by an addition of nitrones on isolated mitochondria extracted from livers not submitted to ischemia-reperfusion. In contrast, mitochondria extracted at the end of the ischemia-reperfusion showed an impairment in the phosphorylation parameters, particularly in the presence of DMPO. Mass spectrum of ischemic liver perchloric acid extracts evidenced probable catabolites in treated groups. The differences in the effect of the two nitrones on energetic metabolism may be explained by the production of deleterious catabolites by DMPO as compared to DEPMPO. Even though a specific radical scavenging effect could be operative in the liver, our results indicate that catabolic effects were predominant. The absence of deleterious effects of DEPMPO in contrast to DMPO on the liver energetic metabolism was evidenced, allowing the use of DEPMPO for ESR detection.     

Pilot tone-based prospective correction of respiratory motion for free-breathing myocardial T1 mapping

Objective

To provide respiratory motion correction for free-breathing myocardial T1 mapping using a pilot tone (PT) and a continuous golden-angle radial acquisition.

Materials and methods

During a 45 s prescan the PT is acquired together with a dynamic sagittal image covering multiple respiratory cycles. From these images, the respiratory heart motion in head-feet and anterior–posterior direction is estimated and two linear models are derived between the PT and heart motion. In the following scan through-plane motion is corrected prospectively with slice tracking based on the PT. In-plane motion is corrected for retrospectively. Our method was evaluated on a motion phantom and 11 healthy subjects.

Results

Non-motion corrected measurements using a moving phantom showed T1 errors of 14 ± 4% (p < 0.05) compared to a reference measurement. The proposed motion correction approach reduced this error to 3 ± 4% (p < 0.05). In vivo the respiratory motion led to an overestimation of T1 values by 26 ± 31% compared to breathhold T1 maps, which was successfully corrected to an average difference of 3 ± 2% (p < 0.05) between our free-breathing approach and breathhold data.

Discussion

Our proposed PT-based motion correction approach allows for T1 mapping during free-breathing with the same accuracy as a corresponding breathhold T1 mapping scan.

     

Cervical carcinoma: standard and pharmacokinetic analysis of time-intensity curves for assessment of tumor angiogenesis and patient survival

Since detailed knowledge regarding the pathophysiological properties—which in turn are responsible for differences in contrast enhancement—remain fairly undetermined, it was the aim of this study (i) to examine the association of standard and pharmacokinetic analysis of time-intensity curves in dynamic MRI with histomorphological markers of tumor angiogenesis (microvessel density [MVD]; vascular endothelial growth factor [VEGF]) and (ii) to determine the ultimate value of a histomorphological and a dynamic MRI approach by correlation of those data with disease outcome in patients with primary cancer of the uterine cervix. Pharmacokinetic parameters (amplitude A, exchange rate constantk ₂₁) and standard parameters (maximum signal intensity (SI)-increase, [SI-I] over baseline and steepest SI-upslope, per second [SI-U/s]) were calculated from contrast-enhanced dynamic MR imaging series in 37 patients with biopsy-proven primary cervical cancer. On the surgical whole mount specimens, histomorphological markers of tumor angiogenesis (MVD, VEGF) were compared with similar sized and positioned regions-of-interest (ROIs) on the MRI-derived parameters. For MRI and histomorphological data, Kaplan-Meier survival curves were calculated and compared using log-rank statistics. A significant association was found betweenMVD and amplitudeA (P<0.01) andSI-I (P<0.05). No significant relationships were observed between theVEGF expression and all dynamic MRI parameters. Kaplan-Meier curves based onk ₂₁ and SI-U/s showed that tumors with highk ₂₁ andSI-U/s values had a significantly (P<0.05, 0.001, respectively) worse disease outcome than tumors with lowk ₂₁ andSI-U/s values. None of the histomorphological gold standard markers for assessing tumor angiogenesis (MVD, VEGF) had any significant power to predict patient survival. It is concluded that (1) the pathophysiological basis for differences in dynamic MRI isMVD but not VEGF-expression; (2) a functional, dynamic MRI approach (both standard and a pharmacokinetic analysis) may be better suited to assess angiogenic activity in terms of patient survival than current histomorphological-based markers of tumor angiogenesis; and [3] compared with standard analysis, a simple pharmacokinetic analysis of time-intensity curves is not superior to assessMVD or patient survival.     

The feasibility of a novel limited field of view spiral cine DENSE sequence to assess myocardial strain in dilated cardiomyopathy

Objective

Develop an accelerated cine displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) sequence to enable clinically feasible myocardial strain evaluation in patients with dilated cardiomyopathy (DCM).

Materials and methods

A spiral cine DENSE sequence was modified by limiting the field of view in two dimensions using in-plane slice-selective pulses in the stimulated echo. This reduced breath hold duration from 20RR to 14RR intervals. Following phantom and pilot studies, the feasibility of the sequence to assess peak radial, circumferential, and longitudinal strain was tested in control subjects (n = 18) and then applied in DCM patients (n = 29).

Results

DENSE acquisition was possible in all participants. Elements of the data were not analysable in 1 control (6%) and 4 DCM r(14%) subjects due to off-resonance or susceptibility artefacts and low signal-to-noise ratio. Peak radial, circumferential, short-axis contour strain and longitudinal strain was reduced in DCM patients (p < 0.001 vs. controls) and strain measurements correlated with left ventricular ejection fraction (with circumferential strain r = − 0.79, p < 0.0001; with vertical long-axis strain r = − 0.76, p < 0.0001). All strain measurements had good inter-observer agreement (ICC > 0.80), except peak radial strain.

Discussion

We demonstrate the feasibility of CMR strain assessment in healthy controls and DCM patients using an accelerated cine DENSE technique. This may facilitate integration of strain assessment into routine CMR studies.

     

Tissue oxygen tension measurements in the Shionogi model of prostate cancer using 19 F MRS and MRI

Objectives: To investigate changes in tumour tissue oxygenation throughout the tumour growth–regression–relapse cycle in an androgen-dependent animal tumour model. Materials and methods: ¹⁹F T₁ relaxometry of Perfluoro-15-Crown-5-Ether was used to measure in vivo partial oxygen pressure (pO₂) of Shionogi tumours on a 2.35-T MR scanner. Perfluoro-15-Crown-5-Ether was administered as an emulsion injected intravenously or as a neat compound injected directly into the tumour. Non-localized, tumour ¹⁹F T₁ measurements, made at multiple time points throughout the tumour cycle, were translated into pO₂ levels. Results: No correlation between tumour size and pO₂ values was found. Values of pO₂ for growing tumours (50 ± 30 torr) were significantly lower than for regressing and relapsing tumours after 9 days post-castration (70 ± 10 torr, p<0.05). Maximum pO₂ values (90 ± 30 torr) were reached between fifth and eighth day post-castration, when tumour pO₂ was significantly higher than both pre-castration (p<0.001) and after 9 days post-castration (p<0.05). Conclusion: We demonstrate that longitudinal pO₂ measurements in vivo are feasible. Values of pO₂ for growing androgen-dependent tumours were significantly lower than for regressing and relapsing androgen-independent tumours. These results have potential clinical importance in optimizing the timing of chemotherapy and/or radiotherapy of hormone dependent tumours.     

Age and gender related effects on adipose tissue compartments of subjects with increased risk for type 2 diabetes: a whole body MRI / MRS study

Quantitative measurement of adipose tissue (AT) compartments in the entire body and of lipids in muscle and liver cells by means of MRI and MRS. Assessment of ageand gender related differences in AT compartments and determination of cross-correlations between AT compartments in a heterogeneous cohort at increased risk for metabolic diseases. One hundred and fifty healthy volunteers with increased risk to type 2 diabetes were examined. T1-weighted MRI was applied for whole-body adipose tissue quantification. Adipose tissue compartments were subdivided in lower extremities, trunk (abdominal subcutaneous (SCAT) and visceral (VAT) adipose tissue), and upper extremities. Intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) in tibialis anterior and soleus muscle were determined by volume selective MRS. Females are characterized by lower %VAT (2.8±1.3% vs. 4.6±1.4% ,p<0.001) and higher %SCAT (14.7±3.9% vs. 9.3±2.9% ,p<0.001). There is a strong correlation between %VAT and age (r=0.64/0.60 for females/males), whereas %SCAT remained virtually unchanged in males (r=-0.09) and was only slightly increaseding in females (r =0.30,p<0.01). For IHCL, age related differences were observed in females with significantly increased IHCL in the older women, but not in males. IMCL contents in both muscles were found almost independent of age in both, males and females. Furthermore, VAT and IHCL show significant correlations in both groups. Assessed age and gender related differences, especially the age related significant increase of VAT and IHCL, as well as cross-correlations between different lipid compartments might contribute to a better understanding of the lipid metabolism under normal and pathologic metabolic conditions in humans.Supported through a grant from the Deutsche Forschungsgemeinschaft (DFG, KFO 114/1)     

On the realizability of non-rational positive real functions

The paper deals with the analysis and synthesis of passive reciprocal one-ports composed of an infinite number of conventional elements (positive R, L. C and ideal transformers), considered as equivalent circuits of physical distributed one-ports. In the generalization from finite to infinite networks, several (generally overlooked) basic difficulties arise, which are discussed and partially clarified. Physically, a prescribed positive real function z(p) is only specified in Rep > 0, and a lossless infinite realization always exists. Since the value of the function in Re p < 0 is then deduced by z(p) + z(–p) = 0, the resistance r(α, ω) = Re z(α + jω) is such that r(0, ω) = 0, but the limit of r(α, ω) for α = +0 may be strictly positive, so that a lossless impedance may have a resistive behaviour in steady-state. The classical Foster and Cauer synthesis procedures may consequently all fail for lossless non-rational impedances, whereas the procedures of Darlington and Bott-Duffin (and sometimes Brune) succeed. Since every point is a transmission zero for an odd function, a cascade synthesis with all zeros at p = 1 always works, and explicit expressions for the element values are obtained. Many examples are treated in detail, and their sometimes pathological behaviour in Re p < 0 is discussed.     

Self-consistent calculation for valence subband structure and hole mobility in <Emphasis Type="Italic">p</Emphasis>-channel inversion layers

Using six- and eight-band k⋅p models—with parameters calibrated against the bulk band structure obtained using non-local empirical pseudopotentials—we have employed a new hybrid self-consistent method to calculate the valence subband structure in p-channel inversion layers of InAs, InSb, GaAs, In_0.53Ga_0.47As, and GaSb. This method involves two separate stages: first, density-of-states (DOS) of the three lowest-energy subbands (heavy, light, and split-off holes) is calculated using the triangular-well approximation. Then, the self-consistent calculation is performed using the DOS previously obtained, but shifting each subband by the amount obtained from the self-consistent eigenvalues obtained during the self-consistent iteration. Finally, we present results regarding the hole mobility in Ge p-channel inversion layers. The results are compared to those obtained employing the subband structure computed with the triangular-well approximation and also with experimental data.     

Monitoring the development of hepatocellular carcinoma in woodchucks using 31P-MRS

The woodchuck is one of the only lab animal models of chronic viral hepatitis infection and the development of hepatocellular carcinoma. Using this model, changes in tissue energetics in the liver due to the development of hepatocellular carcinoma can be monitored by repeated magnetic resonance imaging and localized phosphorus spectroscopy. Age- and sex-matched control (n=5) and chronically infected (n=5) adult woodchucks were imaged four times in a six-month period in a 7-T horizontal-bore magnet. Using a custom-built doubly tunable quadrature volume coil, sagittal and axial FLASH images (128×128, slice thickness = 5 mm, TR/TE=1000/4.1, 8 averages) were acquired to locate the largest portion of the liver with the least amount of signal contamination from surrounding abdominal muscle. Two-dimensional 31P chemical-shift imaging (2D-CSI) was acquired (16×16 data matrix, 24×24×2 cm³, 1024 data points, 16 averages) for all animals. The extent of liver injury was determined using serum gamma glutamyltransferase (GGT). The livers of infected woodchucks showed a significant increase (p=0.01) in phosphomonoesters (PME):β-adenosine triphosphate (NTP). Chronically infected woodchucks had higher levels of serum GGT compared to uninfected woodchucks (p=0.002). An increase in the PME:β-NTP ratio indicates cellular proliferation within the malignant tumor.