Hua Shan Liu

Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma: dosimetric analysis and implication.

PURPOSE To analyze the correlation of radiation-induced liver disease (RILD) with patient-related and treatment-related dose-volume factors and to describe the probability of RILD by a normal tissue complication probability (NTCP) model for patients with hepatocellular carcinoma (HCC) treated with three-dimensional conformal radiotherapy (3D-CRT). METHODS AND MATERIALS Between November 1993 and December 1999, 93 patients with intrahepatic malignancies were treated with 3D-CRT at our institution. Sixty-eight patients who were diagnosed with HCC and had complete 3D dose-volume data were included in this study. Of the 68 patients, 50 had chronic viral hepatitis before treatment, either type B or type C. According to the Child-Pugh classification for liver cirrhosis, 53 patients were in class A and 15 in class B. Fifty-two patients underwent transcatheter arterial chemoembolization with an interval of at least 1 month between transcatheter arterial chemoembolization and 3D-CRT to allow adequate recovery of hepatic function. The mean dose of radiation to the isocenter was 50.2 +/- 5.9 Gy, in daily fractions of 1.8-2Gy. No patient received whole liver irradiation. RILD was defined as Grade 3 or 4 hepatic toxicity according to the Common Toxicity Criteria of the National Cancer Institute. All patients were evaluated for RILD within 4 months of RT completion. Three-dimensional treatment planning with dose-volume histogram analysis of the normal liver was used to compare the dosimetric difference between patients with and without RILD. Maximal likelihood analysis was conducted to obtain the best estimates of parameters of the Lyman NTCP model. Confidence intervals of the fitted parameters were estimated by the profile likelihood method. RESULTS Twelve of the 68 patients developed RILD after 3D-CRT. None of the patient-related variables were significantly associated with RILD. No difference was found in tumor volume (780 cm(3) vs. 737 cm(3), p = 0.86), normal liver volume (1210 cm(3) vs. 1153 cm(3), p = 0.64), percentage of normal liver volume with radiation dose >30 Gy (V(30 Gy); 42% vs. 33%, p = 0.05), and percentage of normal liver volume with >50% of the isocenter dose (V(50%); 45% vs. 36%, p = 0.06) between patients with and without RILD. The mean hepatic dose was significantly higher in patients with RILD (2504 cGy vs. 1965 cGy, p = 0.02). The probability of RILD in patients could be expressed as follows: probability = 1/[1 + exp(-(0.12 x mean dose - 4.29))], with coefficients significantly different from 0. The best estimates of the parameters in the Lyman NTCP model were the volume effect parameter of 0.40, curve steepness parameter of 0.26, and 50% tolerance dose for uniform irradiation of whole liver [TD(50)(1)] of 43 Gy. Patients with RILD had a significantly higher NTCP than did those with no RILD (26.2% vs. 15.8%; p = 0.006), using the best-estimated parameters. CONCLUSION Dose-volume histogram analysis can be effectively used to quantify the tolerance of the liver to RT. Patients with RILD had received a significantly higher mean dose to the liver and a significantly higher NTCP. The fitted volume effect parameter of the Lyman NTCP model was close to that from the literature, but much lower in our patients with HCC and prevalent chronic viral hepatitis than that reported in other series with patients with normal liver function. Additional efforts should be made to test other models to describe the radiation tolerance of the liver for Asian patients with HCC and preexisting compromised hepatic reserve.

Dosimetric analysis and comparison of three-dimensional conformal radiotherapy and intensity-modulated radiation therapy for patients with hepatocellular carcinoma and radiation-induced liver disease.

PURPOSE This study compares the difference in dose-volume data between three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) for patients with hepatocellular carcinoma (HCC) and previously documented radiation-induced liver disease (RILD) after 3D-CRT. MATERIALS AND METHODS Between November 1993 and December 1999, 68 patients with HCC were treated with 3D-CRT at our institution. Twelve of them were diagnosed with RILD within 4 months of completion of 3D-CRT. RILD was defined as either anicteric elevation of alkaline phosphatase level of at least twofold and nonmalignant ascites, or elevated transaminases of at least fivefold the upper limit of normal or of pretreatment levels. Three-dimensional treatment planning using dose-volume histograms of normal liver was used to obtain the dose-volume data. These 12 patients with RILD were replanned with an IMRT planning system using the five-field (gantry angles 0 degrees, 72 degrees, 144 degrees, 216 degrees, and 288 degrees ) step-and-shoot technique to compare the dosimetric difference in targets and organs at risk between 3D-CRT and IMRT. Mean dose and normal tissue complication probability with literature-cited volume effect parameter of 0.32, curve steepness parameter of 0.15, and TD(50)(1) of 40 Gy, were used for the liver, whereas volume fraction at a given dose level was used for other critical structures. Paired Student t-test with 2-tailed p < 0.05 was used to assess the statistical difference between the two techniques. RESULTS With comparable target coverage between 3D-CRT and five-field step-and-shoot IMRT, IMRT was able to obtain a large dose reduction in the spinal cord (5.7% vs. 33.2%, p = 0.007), and achieved at least similar organ sparing for kidneys and stomach. IMRT had diverse dosimetric effect on liver, with significant reduction in normal tissue complication probability (23.7% vs. 36.6%, p = 0.009), but significant increase in mean dose (2924 cGy vs. 2504 cGy, p = 0.009), as compared with 3D-CRT. CONCLUSIONS IMRT is capable of preserving acceptable target coverage and improving or at least maintaining the nonhepatic organ sparing for patients with HCC and previously diagnosed RILD after 3D-CRT. The true impact of this technique on the liver remains unsettled and may depend on the exact volume effect of this organ.

Systematic Review of Structural and Functional Neuroimaging Findings in Children and Adults with CKD

CKD has been linked with cognitive deficits and affective disorders in multiple studies. Analysis of structural and functional neuroimaging in adults and children with kidney disease may provide additional important insights into the pathobiology of this relationship. This paper comprehensively reviews neuroimaging studies in both children and adults. Major databases (PsychLit, MEDLINE, WorldCat, ArticleFirst, PubMed, Ovid MEDLINE) were searched using consistent search terms, and studies published between 1975 and 2012 were included if their samples focused on CKD as the primary disease process. Exclusion criteria included case reports, chapters, and review articles. This systematic process yielded 43 studies for inclusion (30 in adults, 13 in children). Findings from this review identified several clear trends: (1) presence of cerebral atrophy and cerebral density changes in patients with CKD; (2) cerebral vascular disease, including deep white matter hyperintensities, white matter lesions, cerebral microbleeds, silent cerebral infarction, and cortical infarction, in patients with CKD; and (3) similarities in regional cerebral blood flow between patients with CKD and those with affective disorders. These findings document the importance of neuroimaging procedures in understanding the effect of CKD on brain structure, function, and associated behaviors. Results provide a developmental linkage between childhood and adulthood, with respect to the effect of CKD on brain functioning across the lifespan, with strong implications for a cerebrovascular mechanism contributing to this developmental linkage. Use of neuroimaging methods to corroborate manifest neuropsychological deficits or perhaps to indicate preventive actions may prove useful to individuals with CKD.

Salivary Glands: Echo-Planar versus PROPELLER Diffusion-weighted MR Imaging for Assessment of ADCs

PURPOSE To compare the image distortion and the quantification variation in parotid gland apparent diffusion coefficients (ADCs) on periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) versus echo-planar diffusion-weighted (DW) magnetic resonance (MR) images and to investigate the relationship between parotid gland ADC and parotid gland fat content. MATERIALS AND METHODS This prospective study was approved by a local institutional review board. Written informed consent was obtained from all 33 enrolled healthy volunteers (15 men, 18 women; mean age, 36.4 years +/- 11.8 [standard deviation]). All participants underwent 1.5-T non-fat-saturated and fat-saturated PROPELLER DW MR imaging as well as 1.5-T nonaccelerated and twofold-accelerated echo-planar DW MR imaging. Image distortion on the DW images was qualitatively scored, and parotid ADC was quantitatively analyzed. The correlation between parotid ADC and parotid fat content was evaluated by using linear regression analysis. Wilcoxon signed rank and t tests were used for statistical analysis, with Bonferroni correction applied for multiple comparisons. RESULTS Echo-planar DW images showed distortion, which was completely eliminated on the PROPELLER DW images. The mean parotid ADCs measured with non-fat-saturated PROPELLER (0.670 x 10(-3) mm(2) +/- 0.149), nonaccelerated echo-planar (0.892 x 10(-3) mm(2) +/- 0.128), twofold-accelerated echo-planar (1.088 x 10(-3) mm(2) +/- 0.124), and fat-saturated PROPELLER (1.307 x 10(-3) mm(2) +/- 0.217) DW imaging differed significantly from one another (P < .001 for all comparisons). Parotid ADC had a significant negative correlation with parotid fat content (x) measured at non-fat-saturated PROPELLER DW imaging: ADC = -0.0087x + 1.1173 (r = 0.80, P < .001). CONCLUSION PROPELLER DW imaging pulse sequences can yield distortion-free images for parotid ADC measurements and enable quantitative evaluation of the relationship between parotid ADC and parotid fat content. SUPPLEMENTAL MATERIAL http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.2531082228/-/DC1.

Post-treatment with amphetamine enhances reinnervation of the ipsilateral side cortex in stroke rats

Amphetamine (AM) treatment has been shown to alter behavioral recovery after ischemia caused by embolism, permanent unilateral occlusion of the common carotid and middle cerebral arteries, or unilateral sensorimotor cortex ablation in rats. However, the behavioral results are inconsistent possibly due to difficulty controlling the size of the lesion before treatment. There is also evidence that AM promotes neuroregeneration in the cortex contralateral to the infarction; however, the effects of AM in the ipsilateral cortex remain unclear. The purpose of this study was to employ T2-weighted imaging (T2WI) to establish controlled criteria for AM treatment and to examine neuroregenerative effects in both cortices after stroke. Adult rats were anesthetized, and the right middle cerebral artery was ligated for 90 min to generate lesions in the ipsilateral cortex. Animals were separated into two equal treatment groups (AM or saline) according to the size of infarction, measured by T2WI at 2days after stroke. AM or saline was administered to stroke rats every third day starting on day 3 for 4weeks. AM treatment significantly reduced neurological deficits, as measured by body asymmetry and Bedersons score. T2WI and diffusion tensor imaging (DTI) were used to examine the size of infarction and axonal reinnervation, respectively, before and following treatment on days 2, 10 and 25 after stroke. AM treatment reduced the volume of tissue loss on days 10 and 25. A significant increase in fractional anisotropy ratio was found in the ipsilateral cortex after repeated AM administration, suggesting a possible increase in axonal outgrowth in the lesioned side cortex. Western analysis indicated that AM significantly increased the expression of synaptophysin ipsilaterally and neurofilament bilaterally. AM also enhanced matrix metalloproteinase (MMP) enzymatic activity, determined by MMP zymography in the lesioned side cortex. qRT-PCR was used to examine the expression of trophic factors after the 1st and 2nd doses of AM or saline injection. The expression of BDNF, but not BMP7 or CART, was significantly enhanced by AM in the lesioned side cortex. In conclusion, post-stroke treatment with AM facilitates behavioral recovery, which is associated with an increase in fractional anisotropy activity, enhanced fiber growth in tractography, synaptogenesis, upregulation of BDNF, and MMP activity mainly in the lesioned cortex. Our data suggest that the ipsilateral cortex may be the major target of action in stroke brain after AM treatment.

Volume-Dependent Overestimation of Spontaneous Intracerebral Hematoma Volume by the ABC/2 Formula

Background: Although the ABC/2 formula has been widely used to estimate the volume of intracerebral hematoma (ICH), the formula tends to overestimate hematoma volume. The volume-related imprecision of the ABC/2 formula has not been documented quantitatively. Purpose: To investigate the volume-dependent overestimation of the ABC/2 formula by comparing it with computer-assisted volumetric analysis (CAVA). Material and Methods: Forty patients who had suffered spontaneous ICH and who had undergone non-enhanced brain computed tomography scans were enrolled in this study. The ICH volume was estimated based on the ABC/2 formula and also calculated by CAVA. Based on the ICH volume calculated by the CAVA method, the patients were divided into three groups: group 1 consisted of 17 patients with an ICH volume of less than 20 ml; group 2 comprised 13 patients with an ICH volume of 20 to 40 ml; and group 3 was composed of 10 patients with an ICH volume larger than 40 ml. Results: The mean estimated hematoma volume was 43.6 ml when using the ABC/2 formula, compared with 33.8 ml when using the CAVA method. The mean estimated difference was 1.3 ml, 4.4 ml, and 31.4 ml for groups 1, 2, and 3, respectively, corresponding to an estimation error of 9.9%, 16.7%, and 37.1% by the ABC/2 formula (P<0.05). Conclusion: The ABC/2 formula significantly overestimates the volume of ICH. A positive association between the estimation error and the volume of ICH is demonstrated.

CART peptide induces neuroregeneration in stroke rats.

Utilizing a classic stroke model in rodents, middle cerebral artery occlusion (MCAo), we describe a novel neuroregenerative approach using the repeated intranasal administration of cocaine- and amphetamine-regulated transcript (CART) peptide starting from day 3 poststroke for enhancing the functional recovery of injured brain. Adult rats were separated into two groups with similar infarction sizes, measured by magnetic resonance imaging on day 2 after MCAo, and were treated with CART or vehicle. The CART treatment increased CART level in the brain, improved behavioral recovery, and reduced neurological scores. In the subventricular zone (SVZ), CART enhanced immunolabeling of bromodeoxyuridine, a neural progenitor cell marker Musashi-1, and the proliferating cell nuclear antigen, as well as upregulated brain-derived neurotrophic factor (BDNF) mRNA. AAV–GFP was locally applied to the SVZ to examine migration of SVZ cells. The CART enhanced migration of GFP(+) cells from SVZ toward the ischemic cortex. In SVZ culture, CART increased the size of neurospheres. The CART-mediated cell migration from SVZ explants was reduced by anti-BDNF blocking antibody. Using 1H-MRS (proton magnetic resonance spectroscopy), increases in N-acetylaspartate levels were found in the lesioned cortex after CART treatment in stroke brain. Cocaine- and amphetamine-regulated transcript increased the expression of GAP43 and fluoro-ruby fluorescence in the lesioned cortex. In conclusion, our data suggest that intranasal CART treatment facilitates neuroregeneration in stroke brain.

Frequency stabilization using infinite impulse response filtering for SSFP fMRI at 3T.

The steady‐state free precession (SSFP) method has been shown to exhibit strong potential for distortion‐free functional magnetic resonance imaging (fMRI). One major challenge of SSFP fMRI is that the frequency band corresponding to the highest functional sensitivity is extremely narrow, leading to substantial loss of functional contrast in the presence of magnetic field drifts. In this study we propose a frequency stabilization scheme whereby an RF pulse with small flip angle is applied before each image scan, and the initial phase of the free induction decay (FID) signals is extracted to reflect temporal field drifts. A simple infinite impulse response (IIR) filter is further employed to obtain a low‐pass‐filtered estimate of the central reference frequency for the upcoming scan. Experimental results suggest that the proposed scheme can stabilize the frequency settings in accordance with field drifts, with oscillation amplitudes of <0.5 Hz. Phantom studies showed that both slow drifts and fast fluctuations were prominently reduced, resulting in less than 5% signal variations. Visual fMRI at submillimeter in‐plane resolution further demonstrated 15% activation signals that were nicely registered in the microvessels within the sulci. It is concluded that the IIR‐filtered frequency stabilization is an effective technique for achieving reliable SSFP fMR images at high field strengths. Magn Reson Med 57:369–379, 2007.

Effects of Microvascular Permeability Changes on Contrast-Enhanced T1 and Pharmacokinetic MR Imagings After Ischemia

Background and Purpose— Brain enhancement on contrast-enhanced T1-weighted imaging (CET1-WI) after ischemic stroke is generally accepted as an indicator of the blood–brain barrier disruption. However, this phenomenon usually starts to become visible at the subacute phase. The purpose of this study was to evaluate the time-course profiles of Ktrans, cerebral blood volume (vp), and CET1-WI with early detection of blood–brain barrier changes on Ktrans maps and their role for prediction of subsequent hemorrhagic transformation in acute middle cerebral arterial infarct. Methods— Twenty-six patients with acute middle cerebral arterial stroke and early spontaneous reperfusion, whose MR images were obtained at predetermined stroke stages, were included. T2*-based MR perfusion-weighted images were acquired using the first-pass pharmacokinetic model to derive Ktrans and vp. Parenchymal enhancement observed on maps of Ktrans, vp, and CET1-WI at each stage was compared. Association among these measurements and hemorrhagic transformation was analyzed. Results— Ktrans map showed significantly higher parenchymal enhancement in ischemic parenchyma as compared with that of vp map and CET1-WI at early stroke stages (P<0.05). The increased Ktrans at acute stage was not associated with parenchymal enhancement in CET1-WI at the same stage. Parenchymal enhancement in CET1-WI started to occur at the late subacute stage and tended to be luxury reperfusion–dependent. Patients with hemorrhagic transformation showed higher mean Ktrans values as compared with patients without hemorrhagic transformation (P=0.02). Conclusions— Postischemic brain enhancement on routine CET1-WI seems to be closely related to the luxury reperfusion at the late subacute stage and is not dependent on microvascular permeability changes at the acute stage.

Quantification of Non-Water-Suppressed MR Spectra with Correction for Motion-Induced Signal Reduction

Intrascan subject movement in clinical MR spectroscopic examinations may result in inconsistent water suppression that distorts the metabolite signals, frame‐to‐frame variations in spectral phase and frequency, and consequent reductions in the signal‐to‐noise ratio due to destructive averaging. Frame‐to‐frame phase/frequency corrections, although reported to be successful in achieving constructive averaging, rely on consistent water suppression, which may be difficult in the presence of intrascan motion. In this study, motion correction using non–water‐suppressed data acquisition is proposed to overcome the above difficulties. The time‐domain matrix‐pencil postprocessing method was used to extract water signals from the non–water‐suppressed spectroscopic data, followed by phase and frequency corrections of the metabolite signals based on information obtained from the water signals. From in vivo experiments on seven healthy subjects at 3.0 T, quantification of metabolites using the unsuppressed water signal as a reference showed improved correlation with water‐suppressed data acquired in the absence of motion (R2 = 0.9669; slope = 0.94). The metabolite concentrations derived using the proposed approach were in good agreement with literature values. Computer simulations under various degrees of frequency and phase variations further demonstrated robust performance of the time‐domain postprocessing approach. Magn Reson Med, 2009.