Alterations in degree centrality and functional connectivity in tension-type headache: a resting-state fMRI study.

Previous studies have provided evidence of structural and functional changes in the brains of patients with tension-type headache (TTH). However, investigations of functional connectivity alterations in TTH have been inconclusive. The present study aimed to investigate abnormal intrinsic functional connectivity patterns in patients with TTH through the voxel-wise degree centrality (DC) method as well as functional connectivity (FC) analysis. A total of 33 patients with TTH and 30 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and were enrolled in the final study. The voxel-wise DC method was performed to quantify abnormalities in the local functional connectivity hubs. Nodes with abnormal DC were used as seeds for further FC analysis to evaluate alterations in functional connectivity patterns. In addition, correlational analyses were performed between abnormal DC and FC values and clinical features. Compared with HCs, patients with TTH had higher DC values in the left middle temporal gyrus (MTG.L) and lower DC values in the left anterior cingulate and paracingulate gyri (ACG.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Seed-based FC analyses revealed that patients with TTH showed greater connections between ACG.L and the right cerebellum lobule IX (CR-IX.R), and smaller connections between ACG.L and ACG.L. The MTG.L showed increased FC with the ACG.L, and decreased FC with the right caudate nucleus (CAU.R) and left precuneus (PCUN.L) (GRF, voxel-wise p < 0.05, cluster-wise p < 0.05, two-tailed). Additionally, the DC value of the MTG.L was negatively correlated with the DASS-depression score (p = 0.046, r=-0.350). This preliminary study provides important insights into the pathophysiological mechanisms of TTH.

Correlation Analysis between Retention of Gd-DTPA in the Cystic Area of Brain Metastasis and MRI Signs.

Objective: The aim of this study is to investigate gadolinium-diethylenetriaminepentacetate (Gd-DTPA) retention in the cystic area of brain metastasis and its correlation with MRI signs. Methods: Clinical and MRI data of 76 patients with brain metastasis in the cystic area were collected. The contrast signal intensity (CSI) of the cystic area and edema area in the plain scan, enhanced scan, and plain scan after enhancement within 1 month (hereafter referred to as "enhanced plain scan") were analyzed to determine whether Gd-DTPA was retained in these areas. The lesions with higher CSI values on the enhanced plain scan were classified as the Gd-DTPA retention group and the remaining lesions as the Gd-DTPA-free group. The two groups were compared to determine significant differences in primary lesion type, tumor size, tumor location, capsule wall thickness and morphology, peritumoral edema, and renal function. Results: A total of 123 lesions were detected. The CSI of the enhanced plain scan exceeded that of the plain scan and enhanced scan in the cystic area (P < 0.05). There were 54 lesions (43.9%) with Gd-DTPA retention in the cystic area and 69 lesions (56.1%) without Gd-DTPA retention. Significant differences were observed in tumor size and cystic wall thickness between the two groups (P < 0.05), while no significant differences in primary lesion type, cystic wall shape, peritumoral edema, or function were observed. Conclusion: The retention of Gd-DTPA was found in the cystic area of some brain metastases, which was correlated with tumor size and cystic wall thickness.

Shared and distinct reward neural mechanisms among patients with schizophrenia, major depressive disorder, and bipolar disorder: an effort-based functional imaging study.

Unwillingness to exert effort for rewards has been found in patients with schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BD), but the underlying shared and distinct reward neural mechanisms remain unclear. This study aimed to compare the neural correlates of such impairments across different diagnoses. The neural responses in an effort-expenditure for reward task (EEfRT) were assessed in 20 SCZ patients, 23 MDD patients, 17 BD patients, and 30 healthy controls (HC). The results found shared activation in the cingulate gyrus, the medial frontal gyrus, and the middle frontal gyrus during the EEfRT administration. Compared to HC, SCZ patients exhibited stronger variations of functional connectivity between the right caudate and the left amygdala, the left hippocampus and the left putamen, with increase in reward magnitude. In MDD patients, an enhanced activation compared to HC in the right superior temporal gyrus was found with the increase of reward magnitude. The variations of functional connectivity between the caudate and the right cingulate gyrus, the left postcentral gyrus and the left inferior parietal lobule with increase in reward magnitude were weaker than that found in HC. In BD patients, the degree of activation in the left precuneus was increased, but that in the left dorsolateral prefrontal cortex was decreased with increase in reward probability compared to HC. These findings demonstrate both shared and distinct reward neural mechanisms associated with EEfRT in patients with SCZ, MDD, and BD, implicating potential intervention targets to alleviate amotivation in these clinical disorders.

Amplitude of Low-Frequency Fluctuation in Multiple Frequency Bands in Tension-Type Headache Patients: A Resting-State Functional Magnetic Resonance Imaging Study.

Purpose: Tension-type headache (TTH), the most prevalent primary headache disorder, imposes an enormous burden on the people of the world. The quest to ease suffering from this neurological disorder has sustained research interest. The present study aimed at evaluating the amplitude of low-frequency oscillations (LFOs) of the brain in multiple frequency bands in patients with TTH. Methods: To address this question, 63 participants were enrolled in the study, including 32 TTH patients and 31 healthy controls (HCs). For all the participants, amplitude of low-frequency fluctuation (ALFF) was measured in six frequency bands (conventional frequency bands, 0.01-0.08 Hz; slow-2, 0.198-0.25 Hz; slow-3, 0.073-0.198 Hz; slow-4, 0.027-0.073 Hz; slow-5, 0.01-0.027 Hz; and slow-6, 0-0.01 Hz), and the differences between TTH patients and HCs were examined. To explore the relationship between the altered ALFF brain regions in the six frequency bands and the Visual Analog Scale (VAS) score in the TTH patients, Pearson's correlation analysis was performed. Results: In all the six frequency bands, a decreased ALFF value was detected, and regions showing reduced ALFF values were mostly located in the middle frontal gyrus and superior gyrus. A frequency-dependent alternating characterization of intrinsic brain activity was found in the left caudate nucleus in the slow-2 band of 0.198-0.25 Hz and in the right inferior frontal orbital gyrus in the slow-5 band of 0.01-0.027 Hz. For the correlation results, both the left anterior cingulate and paracingulate gyri and right superior parietal gyrus showed a positive correlation with the VAS score in the slow-4 frequency band of 0.027-0.073 Hz. Conclusion: The ALFF alterations in the brain regions of TTH patients are involved in pain processing. The altered LFOs in the multiple regions may help promote the understanding of the pathophysiology of TTH. These observations could also allow the future treatment of TTH to be more directional and targeted and could promote the development of TTH treatment.

Regional homogeneity alterations in multi-frequency bands in tension-type headache: a resting-state fMRI study.

OBJECTIVES: In this study, we aimed to investigate the spontaneous neural activity in the conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz, and slow-5: 0.01-0.027 Hz) in tension-type headache (TTH) patients with regional homogeneity (ReHo) analyses. METHODS: Thirty-eight TTH patients and thirty-eight healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (RS-fMRI) scanning to investigate abnormal spontaneous neural activity using ReHo analysis in conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz and slow-5: 0.01-0.027 Hz). RESULTS: In comparison with the HC group, patients with TTH exhibited ReHo increases in the right medial superior frontal gyrus in the conventional frequency band (0.01-0.08 Hz). The between group differences in the slow-5 band (0.01-0.027 Hz) highly resembled the differences in the conventional frequency band (0.01-0.08 Hz); even the voxels with increased ReHo were spatially more extensive, including the right medial superior frontal gyrus and the middle frontal gyrus. In contrast, no region showed significant between-group differences in the slow-4 band (0.027-0.073 Hz). The correlation analyses showed no correlation between the ReHo values in TTH patients and VAS scores, course of disease and number of seizures per month in conventional band (0.01-0.08 Hz), slow-4 band (0.027-0.073 Hz), as well as in slow-5 band (0.01-0.027 Hz). CONCLUSIONS: The results showed that the superior frontal gyrus and middle frontal gyrus were involved in the integration and processing of pain signals. In addition, the abnormal spontaneous neural activity in TTH patients was frequency-specific. Namely, slow-5 band (0.01-0.027 Hz) might contain additional useful information in comparison to slow-4 band (0.027-0.073 Hz). This preliminary exploration might provide an objective imaging basis for the understanding of the pathophysiological mechanism of TTH.

The value of ESWAN in diagnosis and differential diagnosis of prostate cancer: Preliminary study.

OBJECTIVE: To evaluate the value of enhanced T2 star-weighted angiography (ESWAN) in diagnosis and differential diagnosis of prostate cancer by comparing the multiple indices of ESWAN in benign prostatic hyperplasia (BPH), prostate cancer (PCa) and the normal peripheral zone (PZ). METHODS: Traditional MRI and ESWAN were performed on forty-nine clinically-diagnosed PCa patients, sixty BPH patients, and forty-six normal adult males. The ESWAN indices (magnitude value, phase value, R2* value and T2* value) measured on different regions of interest (ROIs) were analyzed. Additionally, receiver operating characteristic (ROC) analysis was performed to obtain the area under the curve (AUC), sensitivity, specificity, and optimal cut-off points of PCa and BPH, PCa and PZ respectively. RESULTS: The magnitude value, phase value, R2* value and T2* value of PZ were 1529.43±254.43, 0.0689±0.1619, 16.57±8.11, 82.75±53.87, respectively; the magnitude value, phase value, R2* value, and T2* value of PCa were 1540.18±338.62, -0.0176±0.0919, 26.93±11.31, and 45.99±17.43, respectively; the magnitude value, phase value, R2* value, and T2* value of BPH were 1579.49±285.28, 0.0209±0.0839, 20.69±3.95, and 51.56±8.90, respectively. Compared with normal PZ, phase value of PCa was lower (t=-3.302, P=0.001), R2* value higher (t=5.326, P=0.000), and T2* value lower (t=-4.570, P=0.000); compared with BPH, phase value of PCa was lower (t=-2.261, P=0.026), R2* value higher (t=3.988, P=0.000), and T2* value lower (t=-2.155, P=0.033). When PCa and PZ were distinguished, the AUC of magnitude value, phase value, R2* value, and T2* value were respectively 0.539 (P=0.510), 0.679 (P=0.0007), 0.811 (P<0.0001), and 0.762 (P<0.0001); the diagnosis efficiency of R2* value was higher than that of T2* value (P=0.037), while the diagnosis efficiency of T2* value was equivalent to phase value (P=0.256). When PCa was differentiated from BPH, the AUC of magnitude value, phase value, R2* value, and T2* value were 0.518 (P=0.752), 0.612 (P=0.039), 0.705 (P=0.0001), and 0.685 (P=0.0006), respectively; there was no statistical difference in the diagnostic efficiency of phase value, R2* value, and T2* value. CONCLUSIONS: The phase value, R2* value and T2* value can distinguish PCa and normal PZ, PCa and BPH, so they are valuable for the diagnosis and differential diagnosis of PCa, moreover, the diagnostic efficiency of R2* value is better than other indices.

Bone marrow derived mesenchymal stem cells alleviated brain injury via down-regulation of interleukin-1ß in focal cerebral ischemic rats.

Interleukin-1ß (IL-1ß) plays an important role in brain injury after focal ischemia, and bone marrow-derived mesenchymal stem cells (BMSCs) are capable of reducing the expression of IL-1ß, we investigated the effects of BMSCs transplantation on brain edema and cerebral infarction as well as the underlying mechanisms via IL-1ß. Male Sprague-Dawley rats were randomly divided into five groups: Normal + phosphate-buffered saline (PBS), middle cerebral artery occlusion (MCAO) + PBS, Normal + BMSCs, MCAO + BMSCs and MCAO + IL-1ra (an antagonist of IL-1ß). BMSCs were transplanted 24 hours after MCAO, and brain edema was evaluated by Magnetic Resonance Imaging (MRI) and brain water content method after BMSCs transplantation. The expression of NeuN and AQP4 was analyzed by immunofluorescence staining. Protein level of AQP4 and IL-1ß was detected by western blot analysis 48 hours after transplantation. The results showed that BMSCs transplantation reduced brain edema by measurement of brain water content and ADC Value of MRI, as well as the expression of AQP4 and IL-1ß. It was also found that BMSCs transplantation could alleviate the cerebral infarction volume and neuronal damage. Both the brain edema and the cerebral infarction were associated with IL-1ß expression. In conclusion, BMSCs transplantation was capable of alleviating brain edema as well as reducing cerebral infarction via down-regulation of IL-1ß expression, thus repair the injured brain in focal cerebral ischemic rats.

Neural metabolite changes in corpus striatum after rat multipotent mesenchymal stem cells transplanted in hemiparkinsonian rats by magnetic resonance spectroscopy.

OBJECTIVE: To investigate the biochemical changes in striatum after rat bone marrow mesenchymal stem cells (MSCs) were transplanted into hemiparkinsonian rats and to further confirm the therapeutic effects of rat MSCs for Parkinson's disease (PD). METHODS: 5-bromo-2-deoxyuridine (BrdU)-labeled MSCs were transplanted into the corpus striatum of the 6-hydroxydopamine (6-OHDA)-injected side of six PD model rats. Before and 8 weeks after MSC transplantation, ethological changes in PD rats were assessed. The expression of tyrosine hydroxylase (TH) in substantia nigra (SN) and striatum were measured using immunohistochemical methods. The differentiation of MSCs was detected by double immunofluorescence techniques. The concentrations of neural metabolites of N-acetylaspartate (NAA), choline (Cho) and creatine (Cr) were measured by ¹H-magnetic resonance spectroscopy (MRS). Relative concentrations of NAA/Cr and Cho/Cr were calculated. RESULTS: The behavior of PD rats in rotarod tests improved, and there were statistical differences in TH-positive cells in SN and TH-positive terminals in striatum after the transplantation of BrdU-labeled MSCs. Transplanted MSCs differentiated into MAP-2-positive neurons. Especially compared with pre-MSC transplantation, the neural metabolite NAA/Cr ratio of the 6-OHDA-injected side of the striatum increased (P < 0.05) and the Cho/Cr ratio decreased (P < 0.05). CONCLUSION: MSCs transplantation apparently improves neuronal function in the striatum of PD rats.

[Biochemical changes in striatum of Parkinson's disease rat model observed by modified proton magnetic resonance spectroscopy].

This study was undertaken to observe the biochemical changes in striatum of Parkinson's disease (PD) rat model by modified proton magnetic resonance spectroscopy. 12 SD rats were divided into model (n=7) and control (n=5) groups. At 3 weeks after the injection of 6-hydroxydopamine into right striatum, 1H-MRS on the striatum was taken by modified proton magnetic resonance spectroscopy, and then tyrosine hydroxylase (TH) immunostatining was used to visualize the changes of the neurons in substantia nigra and neurites in striatum. The results showed that TH positive neurons and neurites in the substantia nigra compacts (SNc) and striatum in the normal side of the rat model of PD were decreased (P < 0.05), which proved the successful establishment of PD models. The NAA/Cr ratio of the injected side striatum of model group was lower than that of the normal side (P < 0.05). The ratios of Cho/Cr showed no significant difference between the two sides (P > 0.05). These results indicated that the modified 1.5T 1H-MRS should be a noninvasive technique which could provide useful information about the biochemical metabolites in striatum for the study of PD in rat model.

Diffusion-weighted MRI of hepatic tumor in rats: comparison between in vivo and postmortem imaging acquisitions.

PURPOSE: To determine the feasibility of in vivo diffusion-weighted imaging (DWI) to distinguish between normal liver, viable tumor and necrosis compared to postmortem DWI in a rat model with vascular-targeting treatment. MATERIALS AND METHODS: Fifteen rats with liver implantation of 30 rhabdomyosarcomas were treated with combretastatin A-4-phosphate (CA4P) at 10 mg/kg. Two days after treatment, T2-weighted imaging, precontrast T1-weighted imaging, postcontrast T1-weighted imaging, and DWI were performed in vivo and postmortem with a 1.5T scanner. Apparent diffusion coefficients (ADCs) calculated from DWIs with b values of 0, 50, and 100 seconds/mm2 (ADClow), 500, 750, and 1000 seconds/mm2 (ADChigh), 0, 500, and 1000 seconds/mm2 (ADC3b), and 0-1000 seconds/mm2 (ADC10b) for tumor, liver, therapeutic necrosis, and phantoms were compared and validated with ex vivo microangiographic and histopathologic findings. RESULTS: Except ADClow between tumor and necrosis, in vivo ADCs successfully differentiated liver, viable tumor, and necrosis (P<0.05). Compared to in vivo outcomes, postmortem ADCs significantly dropped in tumor and liver (P<0.05) except ADChigh of tumor, but not in necrosis and phantoms. Compared to ADClow, ADChigh was less affected by vital status. CONCLUSION: Advantageous over postmortem DWI, in vivo DWI provides a noninvasive easy-performing tool for distinguishing between liver, viable tumor, and necrosis. ADClow and ADChigh better reflect tissue perfusion and water diffusion, respectively.

Treatment of rodent liver tumor with combretastatin a4 phosphate: noninvasive therapeutic evaluation using multiparametric magnetic resonance imaging in correlation with microangiography and histology.

OBJECTIVES: To document tumoricidal events after intravenous administration of a vascular targeting agent combretastatin A-4-phosphate (CA4P) in rodent liver tumors by using multiparametric magnetic resonance imaging (MRI) in correlation with microangiography and histopathology. MATERIALS AND METHODS: Thirty rhabdomyosarcomas of 8 to 14 mm in diameter were obtained 16 days after implantation in liver lobes of 15 rats. Using a 1.5T magnet and a 4-channel wrist coil, T2-weighted imaging (T2WI), pre- and postcontrast T1-weighted imaging (T1WI), diffusion-weighted imaging (DWI), and dynamic susceptibility imaging (DSI) with relative blood volume (rBV) and flow (rBF) maps were acquired at baseline, 1 hour, 6 hours, and 48 hours after iv injection of CA4P at 10 mg/kg and vehicle in 9 treated and 6 control rats, respectively. In vivo data including signal intensity (SI), tumor volume, apparent diffusion coefficient (ADC), rBV, and rBF were correlated with ex vivo microangiographic and histopathologic findings. RESULTS: CA4P-treated tumors (n = 18) grew slower than those (n = 12) of controls (P < 0.05), with vascular shutdown evident on CE-T1WI at 1 hour but more prominent at 6 hours. However, enhanced rim occurred in the periphery 48 hours after treatment, indicating neovascularization. ADC map enabled distinction between necrotic and viable tumors. DSI-derived tumoral rBV and rBF decreased significantly at 1 hour through 6 hours and partly recovered at 48 hours. SI-time curve reflected diverse therapeutic responses between tumor and liver. MRI findings were verified by ex vivo techniques. CONCLUSIONS: Clinical MRI allowed monitoring of CA4P-related vascular shutdown, necrosis, and neovascularization of liver tumors in rats. Single dose of CA4P seemed insufficient for tumor eradication because of evident peripheral residue and recurrence.

Microplasmin and tissue plasminogen activator: comparison of therapeutic effects in rat stroke model at multiparametric MR imaging.

PURPOSE: To prospectively compare therapeutic and hemorrhagic effects of microplasmin and tissue plasminogen activator (tPA) in stroke therapy by using multiparametric magnetic resonance (MR) imaging in a photothrombotic rat stroke model. MATERIALS AND METHODS: The animal experiment complied with institutional regulations for laboratory animals. Stroke was induced in rats with photothrombotic occlusion of middle cerebral artery (MCA). T2-weighted, perfusion-weighted (PW), and diffusion-weighted (DW) MR imaging was performed 1 hour and 24 hours after occlusion. On the basis of PW and DW images at 1 hour, 49 rats with cortex and subcortex involvement and with perfusion-diffusion mismatch were randomly assigned into one of four groups: control group, group treated with 7.5 mg microplasmin, group treated with 10 mg/kg microplasmin, or group treated with 10 mg/kg tPA. Agents were intravenously injected 1.5 hours after occlusion. Infarct size and hemorrhagic transformation were assessed with MR imaging and histomorphologic findings. Neurologic deficit was scored. Measurements were statistically analyzed. RESULTS: There were 13 rats in the control group, 13 in the 7.5 mg/kg microplasmin group, nine in the 10 mg/kg microplasmin group, and 14 in the 10 mg/kg tPA group. Despite similar baseline perfusion-diffusion mismatch, histochemically defined total infarct volume was reduced from 25% +/- 5 (standard deviation) in control group to 21% +/- 2, 20% +/- 4, and 20% +/- 5 in 7.5 mg/kg microplasmin, 10 mg/kg microplasmin, and tPA groups, respectively, as similarly shown on T2-weighted, DW, and PW images at 24 hours (P < .05). Cerebral hemorrhage rate at 24 hours was higher in tPA group than in the other three groups. Bederson score of neurologic deficits was significantly reduced in treated groups compared with that in control group. CONCLUSION: Perfusion-diffusion mismatch appeared useful in selecting candidates for thrombolytic therapy. Multiparametric MR imaging allowed noninvasive assessment of effects of microplasmin and tPA in rats; microplasmin had a significantly lower hemorrhagic rate.

Delayed perfusion phenomenon in a rat stroke model at 1.5 T MR: an imaging sign parallel to spontaneous reperfusion and ischemic penumbra?

INTRODUCTION: Delayed perfusion (DP) sign at MR imaging was reported in stroke patients. We sought to experimentally elucidate its relation to spontaneous reperfusion and ischemic penumbra. METHODS: Stroke was induced by photothrombotic occlusion of middle cerebral artery in eight rats and studied up to 72 h using a 1.5 T MR scanner with T2 weighted imaging (T2WI), diffusion weighted imaging (DWI), and dynamic susceptibility contrast-enhanced perfusion weighted imaging (DSC-PWI). Relative signal intensity (rSI), relative lesion volume (rLV), relative cerebral blood flow (rCBF), PWI(rLV)-DWI(rLV) mismatch (penumbra) and DP(rLV) were quantified and correlated with neurological deficit score (NDS), triphenyl tetrazolium chloride (TTC) staining, microangiography (MA) and histopathology. RESULTS: The rSI and rLV characterized this stroke model on different MRI sequences and time points. DSC-PWI reproduced cortical DP in all rats, where rCBF evolved from 88.9% at 1 h through 64.9% at 6 h to 136.3% at 72 h. The PWI(rLV)-DWI(rLV) mismatch reached 10+/-5.4% at 1 h, remained positive through 12 h and decreased to -3.3+/-4.5% at 72 h. The incidence and rLV of the DP were well correlated with those of the penumbra (p<0.01, r(2)=0.85 and p<0.0001, r(2)=0.96, respectively). Shorter DP durations and more collateral arterioles occurred in rats without (n=4) than with (n=4) cortex involvement (p<0.05). Rats without cortex involvement tended to earlier reperfusion and a lower NDS. Microscopy confirmed MRI, MA and TTC findings. CONCLUSIONS: In this rat stroke model, we reproduced clinically observed DP on DSC-PWI, confirmed spontaneous reperfusion, and identified the penumbra extending to 12h post-ischemia, which appeared interrelated.

Liver tumor model with implanted rhabdomyosarcoma in rats: MR imaging, microangiography, and histopathologic analysis.

In compliance with institutional regulations for care and use of laboratory animals, the aim of this study was to establish and characterize a rodent liver tumor model to provide a platform for preclinical assessment of new diagnostic and therapeutic strategies. A rhabdomyosarcoma tumor was implanted in the right and left liver lobes of 20 rats, for a total of 40 tumors. T1- and T2-weighted magnetic resonance (MR) images, diffusion-weighted images, and dynamic susceptibility contrast agent-enhanced perfusion-weighted images were obtained up to 16 days after tumor implantation and were compared with postmortem three-dimensional computed tomographic (CT) images, digital microangiograms, and histopathologic findings. Fifteen tumors were examined with proton ((1)H) MR spectroscopy. All tumors grew, with a mean volume doubling time of 2.2 days +/- 0.9 (standard deviation) and a final size of 591 mm(3)+/- 124. The rhabdomyosarcoma tumor showed hypervascularity at MR imaging, three-dimensional CT, microangiography, and histologic analysis. On dynamic susceptibility contrast-enhanced perfusion-weighted images, the maximum signal intensity decrease differed in time and extent between the tumor and the liver, with a significantly (P < .001) higher relative blood volume, relative blood flow, and permeability value in the tumor than in the liver. With (1)H MR spectroscopy, the rhabdomyosarcoma tumor and the liver featured significant (P < .001) choline and lipid peaks, respectively. Implantation of a rhabdomyosarcoma tumor in the livers of rats is feasible and reproducible, and this animal model seems promising for future testing of new diagnostic and therapeutic strategies.

Magnetic resonance imaging after radiofrequency ablation in a rodent model of liver tumor: tissue characterization using a novel necrosis-avid contrast agent.

We exploited a necrosis-avid contrast agent ECIV-7 for magnetic resonance imaging (MRI) in rodent liver tumors after radiofrequency ablation (RFA). Rats bearing liver rhabdomyosarcoma (R1) were randomly allocated to three groups: group I, complete RFA, group II, incomplete RFA, and group III, sham ablation. Within 24 h after RFA, T1-weighted (T1-w) MRI was performed before and after injection of ECIV-7 at 0.05 mmol/kg and followed up from 6-24 h. Signal intensities (SIs) were measured with relative enhancement (RE) and contrast ratio (CR) calculated. The MRI findings were verified histomorphologically. On plain T1-w MRI the contrasts between normal liver, RFA lesion, residual and/or intact tumor were vague. Early after administration of ECIV-7, the liver SI was strongly enhanced (RE=40-50%), leaving the RFA lesion as a hypointense region in groups I and II. At delayed phase, two striking peri-ablational enhancement patterns appeared (RE=90% and CR=1.89%), i.e., "O" type of hyperintense rim in group I and "C" type of incomplete rim in group II. These MRI manifestations could be proven histologically. In this study, tissue components after RFA could be characterized with discernable contrasts by necrosis-avid contrast agent (NACA)-enhanced MRI, especially at delayed phase. This approach may prove useful for defining the ablated area and identifying residual tumor after RFA.

Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration.

The noninvasive assessment of anticancer treatment efficacy is very important for the improvement of therapeutic window. The purpose of the present study was to evaluate the antitumoral effects of the vascular targeting agent, combretastatin A-4 phosphate (CA-4-P), at selected time points after repeated intraperitoneal drug administrations (25 mg/kg), using diffusion-weighted magnetic resonance imaging (DW-MRI). The experiments were performed during an overall follow-up period of 3 weeks on WAG/Rij rats with subcutaneously growing rhabdomyosarcomas. Each animal served as its own baseline. The DW-MRI studies were quantified by calculating the apparent diffusion coefficient (ADC) for different low and high b-values to separate the effects on tumor vasculature and cellular integrity. The changes in ADC as well as the extent of necrosis development (proportional to the tumor volume), measured on the MR images, were of comparable magnitude after each treatment. All ADC values showed a significant decrease at 6 hours, followed by a significant increase at 2 days for various CA-4-P administrations. DW-MRI allowed us to monitor both reduction in perfusion and changes in the extent of tumor necrosis after CA-4-P injection. Repeated CA-4-P administration retains efficacy in rat rhabdomyosarcomas, with similar findings after each drug administration.

Effect of vascular targeting agent in rat tumor model: dynamic contrast-enhanced versus diffusion-weighted MR imaging.

PURPOSE: To compare dynamic contrast material-enhanced magnetic resonance (MR) imaging and diffusion-weighted MR imaging for noninvasive evaluation of early and late effects of a vascular targeting agent in a rat tumor model. MATERIALS AND METHODS: The study protocol was approved by the local ethics committee for animal care and use. Thirteen rats with one rhabdomyosarcoma in each flank (26 tumors) underwent dynamic contrast-enhanced imaging and diffusion-weighted echo-planar imaging in a 1.5-T MR unit before intraperitoneal injection of combretastatin A4 phosphate and at early (1 and 6 hours) and later (2 and 9 days) follow-up examinations after the injection. Histopathologic examination was performed at each time point. The apparent diffusion coefficient (ADC) of each tumor was calculated separately on the basis of diffusion-weighted images obtained with low b gradient values (ADC(low); b = 0, 50, and 100 sec/mm(2)) and high b gradient values (ADC(high); b = 500, 750, and 1000 sec/mm(2)). The difference between ADC(low) and ADC(high) was used as a surrogate measure of tissue perfusion (ADC(low) - ADC(high) = ADC(perf)). From the dynamic contrast-enhanced MR images, the volume transfer constant k and the initial slope of the contrast enhancement-time curve were calculated. For statistical analyses, a paired two-tailed Student t test and linear regression analysis were used. RESULTS: Early after administration of combretastatin, all perfusion-related parameters (k, initial slope, and ADC(perf)) decreased significantly (P < .001); at 9 days after combretastatin administration, they increased significantly (P < .001). Changes in ADC(perf) were correlated with changes in k (R(2) = 0.46, P < .001) and the initial slope (R(2) = 0.67, P < .001). CONCLUSION: Both dynamic contrast-enhanced MR imaging and diffusion-weighted MR imaging allow monitoring of perfusion changes induced by vascular targeting agents in tumors. Diffusion-weighted imaging provides additional information about intratumoral cell viability versus necrosis after administration of combretastatin.

Rat cerebral ischemia induced with photochemical occlusion of proximal middle cerebral artery: a stroke model for MR imaging research.

A stroke model in rats with photochemically induced thrombosis (PIT) of proximal cerebral middle artery (MCA) is introduced for magnetic resonance imaging (MRI) study. Thirty-seven rats subjected to surgical and optical procedures for inducing the PIT models were scanned using a 1.5-T scanner with T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and contrast-enhanced perfusion-weighted imaging (PWI) at 1 h and 24 h after MCA occlusion. The penumbra evolution and PWI-derived parameters including relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) were monitored; and the relative lesion size (RLS) was compared with the final RLS on the gold standard triphenyl tetrazolium chloride (TTC) staining at 24 h. The results showed that the focal cerebral ischemic lesions were detectable in all rats with different MR approaches. The lesion on PWI at 1 h and on all MR images at 24 h was matched well with that seen on TTC staining; the peri-infarct area decreased from 6.2 +/- 7.2% of the brain volume at 1 h to 0.3 +/- 5.6% at 24 h. Compared to that in the contralateral hemisphere, rCBV in ischemic region was 52.6 +/- 21.4 and 40.0 +/- 15.8% (p > 0.05), and rCBF was 64.6 +/- 11.2 and 47.3 +/- 11.1% (p < 0.05) at 1 h and 24 h respectively. The present PIT model in rats has been successfully adopted for MRI research, which might be feasible for certain stroke studies and should be beneficial for the evaluation on effects of potential diagnostic and therapeutic approaches.