Changes In Apparent Diffusion Coefficient Of Water Research Articles

Contribution of perfusion in piffusion-weighted 1H-MRI of intrahepatic and subcutaneous hepatocellular carcinoma in rat

Hepatocellular carcinoma (HCC) and liver metastases are an increasing problem worldwide. Non-invasive methods for understanding of HCC growth mechanisms are highly desirable. A biexponential model for analysis of non-invasive diffusion-weighted 1 H magnetic resonance imaging (MRI) provides important information about neoplastic transformation in capillary liver tissue perfusion and water molecular diffusion. Fast and slow components of water apparent diffusion coefficient (ADC) were separated in the normal rat liver, intrahepatic, and subcutaneous HCCs. MRI was acquired with a Varian 9.4 T horizontal bore system. The fast component of ADC (ADC fast ), which contributes 38% to total signal in the intrahepatic HCC, was significantly lower compared to normal liver value, while the slow component of ADC did not differ in liver, intrahepatic, and subcutaneous HCCs. A decrease in ADC fast may be caused by restricted perfusion in abnormal tumor microvessels. Thus, a reported earlier decrease in ADC in HCC compared to normal liver was mostly due to a decreased in tumor perfusion rather than a decrease in water diffusion. Subcutaneous HCC showed a very limited vasculature development, which makes the tumor perfusion extremely poor and hypoxic. Simultaneous monitoring of water ADC changes in orthotopic and subcutaneous HCCs may be useful, but a possibility of location-based physiological and metabolic differences must be recognized. Keywords: hepatocellular carcinoma, 1 H-MRI, apparent diffusion coefficient, perfusion, tumor location.

Application of 23Na MRI to Monitor Chemotherapeutic Response in RIF-1 Tumors

Effects of an alkylating anticancer drug, cyclophosphamide (Cp), on 23Na signal intensity (23Na SI) and water apparent diffusion coefficient (ADC) were examined in subcutaneously - implanted radiation-induced fibrosarcoma (RIF-1) tumors by in vivo23Na and 1H magnetic resonance imaging (MRI). MRI experiments were performed on untreated control (n = 5) and Cp-treated (n = 6) C3H mice, once before Cp injection (300 mg/kg) then daily for 3 days after treatment. Tumor volumes were significantly lower in treated animals 2 and 3 days posttreatment. At the same time points, MRI experiments showed an increase in both 23Na SI and water ADC in treated tumors, whereas control tumors did not show any significant changes. The correlation between 23Na SI and water ADC changes was dramatically increased in the Cp-treated group, suggesting that the observed increases in 23Na SI and water ADC were caused by the same mechanism. Histologic sections showed decreased cell density in the regions of increased 23Na and water ADC SI. Destructive chemical analysis showed that Cp treatment increased the relative extracellular space and tumor [Na+]. We conclude that the changes in water ADC and 23Na SI were largely due to an increase in extracellular space. 23Na MRI and 1H water ADC measurements may provide valuable noninvasive techniques for monitoring chemotherapeutic responses.

Application of porous-media theory to the investigation of water ADC changes in rabbit Achilles tendon caused by tensile loading

The water apparent diffusion coefficient (ADC) in rabbit Achilles tendon is anisotropic, diffusion-time dependent, and changes as a function of tensile load. Water ADC changes of tendon under mechanical load are thought to be due to the extrusion of water from the more restricted tendon core to a relatively unrestricted bulk phase at the periphery (rim) of the tendon. Tensile loading may influence water ADC values by changing the spatial separation of restricting barriers (e.g., increasing the tendon fibril packing density). To explore this issue, we have applied porous-media theory to the investigation of water ADC changes in rabbit Achilles tendon under two different mechanical loading conditions (a baseline condition with a minimal tensile stress and a second in which the tensile stress was approximately 1 MPa). Diffusion sensitivity was applied in directions parallel and perpendicular to the long axis of the tendon. The short diffusion-time behavior of the resulting time-dependent ADC curves was used to indirectly infer information regarding the average surface area to volume ratio of the space available for molecular diffusion. From these values, we estimated a 40% reduction in volume available for diffusion in the perpendicular direction after tensile loading, but only a 10% reduction in the parallel direction. These differences are consistent with the known geometry of the tendon microstructure and suggest an increase in fibril packing density upon loading. The long diffusion-time behavior of the time-dependent ADC curves was used to indirectly infer the tortuosity of the diffusion pathways through the interstitial space. The tortuosity in the direction perpendicular to the tendon long axis was approximately 2.5 times greater than that in the parallel direction. Stimulated-echo measurement of the ADC values at longer diffusion times resulted in T 1 spin editing of water with shorter T 1 values (and correspondingly lower ADC values). The resulting increase in water ADC with increasing diffusion time was attributed to multiple components arising from the (overlapping) distribution of T 1 values in the core and rim regions of the tendon.

The influence of preischemic hyperglycemia on acute changes in brain water ADC following focal ischemia in rats

The effect of preischemic hyperglycemia on the acute decline of brain apparent diffusion coefficient of water (ADCw) following cerebral ischemia was studied in a rat model of middle cerebral artery occlusion (MCAO). ADCw was measured by NMR with a newly developed spin-echo line-scan protocol that provides for an ADCw calculation every 15 s at a spatial resolution of 3.4 μl/pixel. A remote controlled occluding device was used to initiate ischemia from outside the magnet, allowing for continuous monitoring of ADCw before, during and after MCAO. Preischemic hyperglycemia (25–30 mM) was achieved via i.v. infusion of 50% glucose. The decline in ADCw following ischemia was analyzed to obtain three-time constants: the time from onset of ischemia to initial significant ADCw decline below baseline level (i.e., 20% of maximal decline, T 0.20), the time to decline by 50% ( T 0.50), and the time to decline by 95% ( T 0.95). Mean (±S.D.) values for T 0.20, T 0.50, T 0.95 were: 39.6±7.2, 54.0±7.8, 105.0±15.0 s for the normoglycemic group ( n=7), and 49.2±33.0, 116.4±2.4, 351.0±189.0 s for the hyperglycemic group ( n=6), respectively. Hyperglycemia significantly prolongs T 0.50 and T 0.95 but does not affect T 0.20. The temporal profiles of ADCw decline following ischemia under normo- and hyperglycemia are distinctively different from the known time course of membrane depolarization under similar experimental conditions, suggesting that mechanisms other than membrane depolarization and cell swelling may contribute to changes in ADCw in cerebral ischemia.

Status of the Neonatal Rat Brain after NMDA-Induced Excitotoxic Injury as Measured by MRI, MRS and Metabolic Imaging

Intrastriatal injection of the excitotoxin N-methyl-dsc-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

Status of the neonatal rat brain after NMDA-induced excitotoxic injury as measured by MRI, MRS and metabolic imaging.

Intrastriatal injection of the excitotoxin N-methyl-D-aspartate (NMDA) in neonatal rat brain resulted in an acute ipsilateral decrease of the apparent diffusion coefficient (ADC) of brain tissue water, as measured with diffusion-weighted MRI. The early diffusion changes were accompanied by only mild changes in the overall metabolic status as measured by in vivo 1H MRS and 31P MRS and metabolic imaging of brain sections. Minimal decreases in the high-energy phosphate levels and a small hemispheric acidosis were observed in the first 6 h after NMDA administration. In addition, there was very modest lactate accumulation. Twenty-four hours after the induction of the excitotoxic injury the tissue energy status was still only moderately affected, whereas an overall decrease of 1H MRS-detected brain metabolites was found. Treatment with the non-competitive NMDA-antagonist MK-801 given within 90 min after NMDA injection rapidly reversed the NMDA-induced changes in the entire ipsilateral hemisphere. The effect of the competitive NMDA-antagonist D-CPPene was restricted to the cortical areas and was accomplished on a slower time scale. Our results indicate that; (i) early excitotoxicity in the neonatal rat brain does not lead to profound changes in the metabolic status; and (ii) brain tissue water ADC changes are not necessarily associated with a metabolic energy failure.

Alteration of Intracellular Metabolite Diffusion in Rat Brain In Vivo During Ischemia and Reperfusion

Diffusion-weighted MRI can demonstrate decreases of the apparent diffusion coefficient (ADC) of brain tissue water shortly after the onset of ischemia. To further elucidate underlying mechanisms, this study extended diffusion assessment to intracellular metabolites in rat brain in vivo before, during, and after ischemia. Changes in molecular mobility were studied in a rat model of global forebrain ischemia (n = 8, 20-minute occlusion, 120-minute reperfusion) with the use of diffusion-weighted localized proton MR spectroscopy. During ischemia and early reperfusion the time course of ADC changes was monitored by strongly diffusion-weighted spectra. ADC values of N-acetylaspartate, creatines, cholines, and myo-inositol were evaluated from series of differently diffusion-weighted spectra before ischemia, 90 minutes after reperfusion, and 60 minutes postmortem. Parallel to a rise in diffusion-weighted water signal (133 +/- 20%), pertinent intensities of all brain metabolites increased during ischemia. Changes were most pronounced for myo-inositol (46 +/- 9%) and smallest for N-acetylaspartate (12 +/- 4%). During reperfusion water ADC values returned to basal values, whereas metabolite ADC values were decreased by 22% (after 40 minutes). Postmortem ADC values (after 60 minutes) were reduced by 46% for water and 38% for metabolites. The present findings indicate that water ADC changes during ischemic stroke are accompanied by significant alterations in intracellular mobility in both neuronal and glial cell populations as reflected by N-acetylaspartate and myo-inositol, respectively. Altered metabolite ADC values during reperfusion are consistent with irreversible tissue damage in this model and offer new means to assess circulatory and metabolic compromise.