• The Korean Journal of Nuclear Medicine Technology
• /
• v.14 no.2
• /
• pp.21-25
• /
• 2010

Purpose: For better PET imaging with accuracy the transmission scanning is inevitably required for attenuation correction. The attenuation is affected by condition of acquisition and patient position, consequently quantitative accuracy may be decreased in emission scan imaging. In this paper, the present study aims at providing the measurement for attenuation varying with the positions of the patient's arm in whole body PET/CT, further performing the comparative analysis over its SUV changes. Materials and Methods: NEMA 1994 PET phantom was filled with $^{18}F$-FDG and the concentration ratio of insert cylinder and background water fit to 4:1. Phantom images were acquired through emission scanning for 4min after conducting transmission scanning by using CT. In an attempt to acquire image at the state that the arm of the patient was positioned at the lower of ahead, image was acquired in away that two pieces of Teflon inserts were used additionally by fixing phantoms at both sides of phantom. The acquired imaged at a were reconstructed by applying the iterative reconstruction method (iteration: 2, subset: 28) as well as attenuation correction using the CT, and then VOI was drawn on each image plane so as to measure CT number and SUV and comparatively analyze axial uniformity (A.U=Standard deviation/Average SUV) of PET images. Results: It was found from the above phantom test that, when comparing two cases of whether Teflon insert was fixed or removed, the CT number of cylinder increased from -5.76 HU to 0 HU, while SUV decreased from 24.64 to 24.29 and A.U from 0.064 to 0.052. And the CT number of background water was identified to increase from -6.14 HU to -0.43 HU, whereas SUV decreased from 6.3 to 5.6 and A.U also decreased from 0.12 to 0.10. In addition, as for the patient image, CT number was verified to increase from 53.09 HU to 58.31 HU and SUV decreased from 24.96 to 21.81 when the patient's arm was positioned over the head rather than when it was lowered. Conclusion: When arms up protocol was applied, the SUV of phantom and patient image was decreased by 1.4% and 9.2% respectively. With the present study it was concluded that in case of PET/CT scanning against the whole body of a patient the position of patient's arm was not so much significant. Especially, the scanning under the condition that the arm is raised over to the head gives rise to more probability that the patient is likely to move due to long scanning time that causes the increase of uptake of $^{18}F$-FDG of brown fat at the shoulder part together with increased pain imposing to the shoulder and discomfort to a patient. As regarding consideration all of such factors, it could be rationally drawn that PET/CT scanning could be made with the arm of the subject lowered.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.14 no.2
• /
• pp.203-207
• /
• 2010

Purpose: Hepatitis B is infection caused by Hepatitis B virus (HBV). Currently, there are several methods, Kits and equipments for conducting Hepatitis B test. Due to ununiformed methods, it would cause some differences. To manage these differences, it needs process evaluating function of test system and reagent using particular standard substance. The aim of this study is to investigate tendency of RIA method's reagent used in Asan Medical Center through comparing several other test reagents using national standard substance. Materials and Methods: The standard substance in National Institute of Food and Drug Safety Evaluation's biology medicine consists of 5 things, 4 antigens and 1 antibody. We tested reagents using A, B company's Kits according to each test method. All tests are measured repeatedly to obtain accurate results. Results: Test result of "HBs Ag Mixed titer Performance panel" is obtained match rate compared S/CO unit standard with RIA method and EIA 3 reagents, CIA 2 reagents is that company A's reagent is 94.4% (17/18), 83.3% (15/18), B is 88.9% (16/18), 77.8% (14/18). Test result of "HBs Ag Low titer Performance panel" is obtain that EIA 2 reagents is shown 7 posive results, CIA 3 reagents is 11, and RIA method's company A's reagent is 3, B is 2 of 13 in low panel. "HBV surface antigen 86.76 IU/vial" tested dilution. A is obtain positive results to 600 times(0.14 IU/mL), B is 300 times (0.29 IU/mL). Case of "HBV human immunoglobulin 95.45 IU/vial", A is shown positive result to 10,000 times (9.5 mIU/mL) and B is 4,000 times (24 mIU/mL). Test result of "HBs Ag Working Standards 0.02~11.52 IU/mL" is shown that Company A's kit concentration level was 0.38IU/mL, company B was 2.23 IU/mL and higher level of concentration was positive results. Conclusion: When comparing various test reagents and RIA method according to National Standard substances for Hepatitis B test, we recognized that there were no significant trends between reagents. For hepatitis B virus antigen-antibody titers even in parts of the test up to 600 times the antigen, antibodies to 10,000 times the maximum positive results could be obtained. Therefore, we confirmed that results from Asan Medical Center are performed smoothly by reagents and system for hepatitis B virus test.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.14 no.2
• /
• pp.122-127
• /
• 2010

Purpose: The Xpress3.$cardiac^{TM}$ which is a kind of wide beam reconstruction (WBR) method developed by UltraSPECT (Haifa, Israel) enables the acquisition of at quarter time while maintaining image quality. The purpose of this study is to investigate the usefulness of WBR method for decreasing scan times and to compare to it with filtered back projection (FBP), which is the method routinely used. Materials and Methods: Phantom and clinical studies were performed. The anthropomorphic torso phantom was made on an equality with counts from patient's body. The Tl-201 concentrations in the compartments were 74 kBq (2 ${\mu}Ci$)/cc in myocardium, 11.1 kBq (0.3 ${\mu}Ci$)/cc in soft tissue, and 2.59 kBq (0.07 ${\mu}Ci$)/cc in lung. The non-gated Tl-201 myocardial perfusion SPECT data were acquired with the phantom. The former study was scanned for 50 seconds per frame with FBP method, and the latter study was acquired for 13 seconds per frame with WBR method. Using the Xeleris ver. 2.0551, full width at half maximum (FWHM) and average image contrast were compared. In clinical studies, we analyzed the 30 patients who were examined by Tl-201 gated myocardial perfusion SPECT in department of nuclear medicine at Asan Medical Center from January to April 2010. The patients were imaged at full time (50 second per frame) with FBP algorithm and again quarter-time (13 second per frame) with the WBR algorithm. Using the 4D MSPECT (4DM), Quantitative Perfusion SPECT (QPS), and Quantitative Gated SPECT (QGS) software, the summed stress score (SSS), summed rest score (SRS), summed difference score, end-diastolic volume (EDV), end-systolic volume (ESV) and ejection fraction (EF) were analyzed for their correlations and statistical comparison by paired t-test. Results: As a result of the phantom study, the WBR method improved FWHM more than about 30% compared with FBP method (WBR data 5.47 mm, FBP data 7.07 mm). And the WBR method's average image contrast was also higher than FBP method's. However, in result of quantitative indices, SSS, SDS, SRS, EDV, ESV, EF, there were statistically significant differences from WBR and FBP(p<0.01). In the correlation of SSS, SDS, SRS, there were significant differences for WBR and FBP (0.18, 0.34, 0.08). But EDV, ESV, EF showed good correlation with WBR and FBP (0.88, 0.89, 0.71). Conclusion: From phantom study results, we confirmed that the WBR method reduces an acquisition time while improving an image quality compared with FBP method. However, we should consider significant differences in quantitative indices. And it needs to take an evaluation test to apply clinical study to find a cause of differences out between phantom and clinical results.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.14 no.2
• /
• pp.110-116
• /
• 2010

Purpose: The X-ray attenuation coefficient based on CT images is used for attenuation correction in PET/CT. The polychromatic X-ray beam can introduce beam-hardening artifact on CT images. The aims of the study were to evaluate the effect of dental metal prostheses in phantom and patients on apparent tracer activity measured with PET/CT when using CT attenuation correction. Materials and Methods: 40 normal patients (mean age $54{\pm}12$) was scanned between Jan and Feb 2010. NEMA(National Electrical Manufactures Association) PET $Phantom^{TM}$ (NU2-1994) was filled with $^{18}F$-FDG injected into the water that insert implant and metal prostheses dental cast. Region of interest were drawn in non-artifact region, bright steak artifact region and dark streak artifact region on the same transaxial CT and PET slices. Patients and phantom with dental metal prostheses and dental implant were evaluated the change rate of CT Number and $SUV_{mean}$ in PET/CT. A paired t-test was performed to compare the ratio and the difference of the calculated values. Results: In patients with dental metal prostheses, $SUV_{mean}$ was reduced 19.64% (p<0.05) in the non-steak artifact region than the brightstreak artifact region whereas was increased 90.1% (p>0.05) in the non-steak artifact region than the dark streak artifact region. In phantom with dental metal prostheses, $SUV_{mean}$ was reduced 18.1% (p<0.05) in the non-steak artifact region than the bright streak artifact region whereas was increased 18.0% (p>0.05) in the non-steak artifact region than the dark streak artifact region. In patients with dental implant, $SUV_{mean}$ was increased 19.1% (p<0.05) in the non-steak artifact region than the bright streak artifact region whereas was increased 96.62% (p>0.05) in the non-steak artifact region than the dark streak artifact region. In phantom with dental implant, $SUV_{mean}$ was increased 14.4% (p<0.05) in the non-steak artifact region than the bright streak artifact region whereas was increased 7.0% (p>0.05) in the non-steak artifact region than the dark streak artifact region. Conclusion: When CT is used for attenuation correction in patients with dental metal prostheses, 19.1% reduced $SUV_{mean}$ is anticipated in the dark streak artifact region on CT images. The dark streak artifacts of CT by dental metal prostheses may cause false negative finding in PET/CT. We recommend that the non-attenuation corrected PET images also be evaluated for clinical use.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.20 no.2
• /
• pp.3-8
• /
• 2016

Purpose SUV is one of the parameters that assist diagnosis in origin, metastasis and staging of cancer. Specially, it is important to compare SUV before and after chemo or radiation therapy to find out effectiveness of treatment. Storing PET data which has no quantitative change is needed for SUV comparison. However, there is a possibility to loss the data in external hard drive or MINIpacs that are managed by department of nuclear medicine. The aim of this study is to evaluate SUV and metabolic tumor volume (MTV) among reconstructed data (R-D) in workstation, R-D and re-sliced data (S-D) in PACS. Materials and Methods Data of 20 patients (aged $60.5{\pm}8.3y$) underwent $^{18}F-FDG$ PET (Biograph truepoint 40, mCT 40, mCT 64, mMR, Siemens) study were analysed. $SUV_{max}$, $SUV_{peak}$ and MTV were measured in liver, aorta and tumor after sending R-D in workstation, R-D and S-D in PACS to syngo.via software. Results R-D of workstation and PACS showed the same value as mean $SUV_{max}$ in liver, aorta and tumor were $2.95{\pm}0.59$, $2.35{\pm}0.61$, $10.36{\pm}6.15$ and $SUV_{peak}$ were $2.70{\pm}0.51$, $2.07{\pm}0.43$, $7.67{\pm}3.73$(p>0.05) respectively. Mean $SUV_{max}$ of S-D in PACS were decreased by 5.18%, 7.22%, 12.11% and $SUV_{peak}$ 2.61%, 3.63%, 10.07%(p<0.05). Correlation between R-D and S-D were $SUV_{max}$ 0.99, 0.96, 0.99 and $SUV_{peak}$ 0.99, 0.99, 0.99. And 2SD in balnd-altman analysis were $SUV_{max}$ 0.125, 0.290, 1.864 and $SUV_{peak}$ 0.053, 0.103, 0.826. MTV of R-D in workstation and PACS show the same value as $14.21{\pm}12.72cm^3$(p>0.05). MTV in PACS was decreased by 0.12% compared to R-D(p>0.05). Correlation and 2SD between R-D and S-D were 0.99 and 2.243. Conclusion $SUV_{max}$, $SUV_{peak}$, MTV showed the same value in both of R-D in workstation and PACS. However, there was statistically difference in $SUV_{max}$, $SUV_{peak}$ of S-D compare to R-D despite of high correlation. It is possible to analyse reliable pre and post SUV if storing R-D in main hospital PACS system.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.22 no.1
• /
• pp.90-97
• /
• 2018

Purpose The lung segment ratio which is obtained through quantitative analyses of lung perfusion scan images is calculated to evaluate the lung function pre and post surgery. In this Study, the planar image production methods by using Q-Metrix (GE Healthcare, USA) program capable of not only quantitative analysis but also computation of the segment ratio after having performed SPECT/CT are comparatively evaluated. Materials and Methods Lung perfusion scan and SPECT/CT were performed on 50 lung cancer patients prior to surgery who visited our hospital from May 1, 2015 to September 13, 2016 by using Discovery 670(GE Healthcare, USA) equipment. AP(Anterior Posterior)method that uses planar image divided the frontal and rear images into three rectangular portions by means of ROI tool while PO(Posterior Oblique)method computed the segment ratio by dividing the right lobe into three parts and the left lobe into two parts on the oblique image. Segment ratio was computed by setting the ROI and VOI in the CT image by using Q-Metrix program and statistically analysis was performed with SPSS Ver. 23. Results Regarding the correlation concordance rate of Q-Metrix and AP methods, RUL(Right upper lobe), RML(Right middle lobe) and RLL(Right lower lobe) were 0.224, 0.035 and 0.447. LUL(Left upper lobe) and LLL(Left lower lobe) were found to be 0.643 and 0.456, respectively. In the PO method, the right lobe were 0.663, 0.623 and 0.702, respectively, while the left lobe were 0.754 and 0.823. When comparison was made by using the Paired sample T-test, Right lobe were $11.6{\pm}4.5$, $26.9{\pm}6.2$ and $17.8{\pm}4.2$, respectively in the AP method. Left lobe were $28.4{\pm}4.8$ and $15.4{\pm}5.6$. The right lobe of PO had values of $17.4{\pm}5.0$, $10.5{\pm}3.6$ and $27.3{\pm}6.0$, while the left lobe had values of $21.6{\pm}4.8$ and $23.1{\pm}6.6$, thereby having statistically significant difference in comparison to the Q-Metrix method for each of the lobes (P<0.05). However, there was no statistically significant difference in Right middle lobe (P>0.05). Conclusion The AP method showed low concordance rate in correlation with the Q-Metrix method. However, PO method displayed high concordance rate overall. although AP method had significant differences in all lobes, there was no significant difference in Right middle lobe of PO method. Therefore, at the time of production of lung perfusion scan results, utilization of Q-Metrix method of SPECT/CT would be useful in computation of accurate resultant values. Moreover, it is deemed possible to expect obtain more practical sectional computation result values by using PO method at the time of planar image acquisition.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.22 no.1
• /
• pp.55-66
• /
• 2018

Purpose In PET/CT exam, washed-out artifact could occur due to severe motion of the patient and high specific activity, it results in lowering not only qualitative reading but also quantitative analysis. Scatter limitation correction by GE is an algorism to correct washed-out artifact and recover the images in PET scan. The purpose of this study is to measure the threshold of specific activity which can recovers to original uptake values on the image shown with washed-out artifact from phantom experiment and to compare the quantitative analysis of the clinical patient's data before and after correction. Materials and Methods PET and CT images were acquired in having no misalignment(D0) and in 1, 2, 3, 4 cm distance of misalignment(D1, D2, D3, D4) respectively, with 20 steps of each specific activity from 20 to 20,000 kBq/ml on $^{68}Ge$ cylinder phantom. Also, we measured the distance of misalignment of foley catheter line between CT and PET images, the specific activity which makes washed-out artifact, $SUV_{mean}$ of muscle in artifact slice and $SUV_{max}$ of lesion in artifact slice and $SUV_{max}$ of the other lesion out of artifact slice before and after correction respectively from 34 patients who underwent $^{18}F-FDG$ Fusion Whole Body PET/CT exam. SPSS 21 was used to analyze the difference in the SUV between before and after scatter limitation correction by paired t-test. Results In phantom experiment, $SUV_{mean}$ of $^{68}Ge$ cylinder decreased as specific activity of $^{18}F$ increased. $SUV_{mean}$ more and more decreased as the distance of misalignment between CT and PET more increased. On the other hand, the effect of correction increased as the distance more increased. From phantom experiments, there was no washed-out artifact below 50 kBq/ml and $SUV_{mean}$ was same from origin. On D0 and D1, $SUV_{mean}$ recovered to origin(0.95) below 120 kBq/ml when applying scatter limitation correction. On D2 and D3, $SUV_{mean}$ recovered to origin below 100 kBq/ml. On D4, $SUV_{mean}$ recovered to origin below 80 kBq/ml. From 34 clinical patient's data, the average distance of misalignment was 2.02 cm and the average specific activity which makes washed-out artifact was 490.15 kBq/ml. The average $SUV_{mean}$ of muscles and the average $SUV_{max}$ of lesions in artifact slice before and after the correction show a significant difference according to a paired t-test respectively(t=-13.805, p=0.000)(t=-2.851, p=0.012), but the average $SUV_{max}$ of lesions out of artifact slice show a no significant difference (t=-1.173, p=0.250). Conclusion Scatter limitation correction algorism by GE PET/CT scanner helps to correct washed-out artifact from motion of a patient or high specific activity and to recover the PET images. When we read the image occurred with washed-out artifact by measuring the distance of misalignment between CT and PET image, specific activity after applying scatter limitation algorism, we can analyze the images more accurately without repeating scan.

• Radiation Oncology Journal
• /
• v.20 no.1
• /
• pp.41-52
• /
• 2002

Purpose : 3D conformal radiotherapy, the optimum dose delivered to the tumor and provided the risk of normal tissue unless marginal miss, was restricted by organ motion. For tumors in the thorax and abdomen, the planning target volume (PTV) is decided including the margin for movement of tumor volumes during treatment due to patients breathing. We designed the respiratory gating radiotherapy device (RGRD) for using during CT simulation, dose planning and beam delivery at identical breathing period conditions. Using RGRD, reducing the treatment margin for organ (thorax or abdomen) motion due to breathing and improve dose distribution for 3D conformal radiotherapy. Materials and Methods : The internal organ motion data for lung cancer patients were obtained by examining the diaphragm in the supine position to find the position dependency. We made a respiratory gating radiotherapy device (RGRD) that is composed of a strip band, drug sensor, micro switch, and a connected on-off switch in a LINAC control box. During same breathing period by RGRD, spiral CT scan, virtual simulation, and 3D dose planing for lung cancer patients were peformed, without an extended PTV margin for free breathing, and then the dose was delivered at the same positions. We calculated effective volumes and normal tissue complication probabilities (NTCP) using dose volume histograms for normal lung, and analyzed changes in doses associated with selected NTCP levels and tumor control probabilities (TCP) at these new dose levels. The effects of 3D conformal radiotherapy by RGRD were evaluated with DVH (Dose Volume Histogram), TCP, NTCP and dose statistics. Results : The average movement of a diaphragm was 1.5 cm in the supine position when patients breathed freely. Depending on the location of the tumor, the magnitude of the PTV margin needs to be extended from 1 cm to 3 cm, which can greatly increase normal tissue irradiation, and hence, results in increase of the normal tissue complications probabiliy. Simple and precise RGRD is very easy to setup on patients and is sensitive to length variation (+2 mm), it also delivers on-off information to patients and the LINAC machine. We evaluated the treatment plans of patients who had received conformal partial organ lung irradiation for the treatment of thorax malignancies. Using RGRD, the PTV margin by free breathing can be reduced about 2 cm for moving organs by breathing. TCP values are almost the same values $(4\~5\%\;increased)$ for lung cancer regardless of increasing the PTV margin to 2.0 cm but NTCP values are rapidly increased $(50\~70\%\;increased)$ for upon extending PTV margins by 2.0 cm. Conclusion : Internal organ motion due to breathing can be reduced effectively using our simple RGRD. This method can be used in clinical treatments to reduce organ motion induced margin, thereby reducing normal tissue irradiation. Using treatment planning software, the dose to normal tissues was analyzed by comparing dose statistics with and without RGRD. Potential benefits of radiotherapy derived from reduction or elimination of planning target volume (PTV) margins associated with patient breathing through the evaluation of the lung cancer patients treated with 3D conformal radiotherapy.

• Radiation Oncology Journal
• /
• v.25 no.1
• /
• pp.7-15
• /
• 2007

[ $\underline{Purpose}$ ]: To determine the patterns of evaluation and treatment in patients with breast cancer after mastectomy and treated with radiotherapy. A nationwide study was performed with the goal of improving radiotherapy treatment. $\underline{Materials\;and\;Methods}$: A web- based database system for the Korean Patterns of Care Study (PCS) for 6 common cancers was developed. Randomly selected records of 286 eligible patients treated between 1998 and 1999 from 17 hospitals were reviewed. $\underline{Results}$: The ages of the study patients ranged from 20 to 80 years (median age 44 years). The pathologic T stage by the AJCC was T1 in 9.7% of the cases, T2 in 59.2% of the cases, T3 in 25.6% of the cases, and T4 in 5.3% of the cases. For analysis of nodal involvement, N0 was 7.3%, N1 was 14%, N2 was 38.8%, and N3 was 38.5% of the cases. The AJCC stage was stage I in 0.7% of the cases, stage IIa in 3.8% of the cases, stage IIb in 9.8% of the cases, stage IIIa in 43% of the cases, stage IIIb in 2.8% of the cases, and IIIc in 38.5% of the cases. There were various sequences of chemotherapy and radiotherapy after mastectomy. Mastectomy and chemotherapy followed by radiotherapy was the most commonly performed sequence in 47% of the cases. Mastectomy, chemotherapy, and radiotherapy followed by additional chemotherapy was performed in 35% of the cases, and neoadjuvant chemoradiotherapy was performed in 12.5% of the cases. The radiotherapy volume was chest wall only in 5.6% of the cases. The volume was chest wall and supraclavicular fossa (SCL) in 20.3% of the cases; chest wall, SCL and internal mammary lymph node (IMN) in 27.6% of the cases; chest wall, SCL and posterior axillary lymph node in 25.9% of the cases; chest wall, SCL, IMN, and posterior axillary lymph node in 19.9% of the cases. Two patients received IMN only. The method of chest wall irradiation was tangential field in 57.3% of the cases and electron beam in 42% of the cases. A bolus for the chest wall was used in 54.8% of the tangential field cases and 52.5% of the electron beam cases. The radiation dose to the chest wall was $45{\sim}59.4\;Gy$ (median 50.4 Gy), to the SCL was $45{\sim}59.4\;Gy$ (median 50.4 Gy), and to the PAB was $4.8{\sim}38.8\;Gy$, (median 9 Gy) $\underline{Conclusion}$: Different and various treatment methods were used for radiotherapy of the breast cancer patients after mastectomy in each hospital. Most of treatment methods varied in the irradiation of the chest wall. A separate analysis for the details of radiotherapy planning also needs to be followed and the outcome of treatment is needed in order to evaluate the different processes.

• The Korean Journal of Nuclear Medicine
• /
• v.37 no.6
• /
• pp.418-427
• /
• 2003

Objects: $^{99m}-lactosylated$ human serum albumin (LSA) is a newly synthesized radiopharmaceutical that binds to asialoglycoprotein receptors, which are specifically presented on the hepatocyte membrane. Hepatic uptake and blood clearance of LSA were evaluated in rat with acute hepatic injury induced by dimethylnitrosamine (DMN) and results were compared with corresponding findings of liver enzyme profile and these of histologic changes. Materials and Methods: DMN (27 mg/kg) was injected intraperitoneally in Sprague-Dawley rat to induce acute hepatic injury. At 3(DMN-3), 8(DMN-8), and 21 (DMN-21) days after injection of DMN, LSA injected intravenously, and dynamic images of the liver and heart were recorded for 30 minutes. Time-activity curves of the heart and liver were generated from regions of interest drawn over liver and heart area. Degree of hepatic uptake and blood clearance of LSA were evaluated with visual interpretation and semiquantitative analysis using parameters (receptor index : LHL3 and index of blood clearance : HH3), analysis of time-activity curve was also performed with curve fitting using Prism program. Results: Visual assessment of LSA images revealed decreased hepatic uptake in DMN treated rat, compared to control group. In semiquantitative analysis, LHL3 was significantly lower in DMN treated rat group than control rat group (DMN-3: 0.842, DMN-8: 0.898, DMN-21: 0.91, Control: 0.96, p<0.05), whereas HH3 was significantly higher than control rat group (DMN-3: 0.731,.DMN-8: 0.654, DMN-21: 0.604, Control: 0.473, p<0.05). AST and ALT were significantly higher in DMN-3 group than those of control group. Centrilobular necrosis and infiltration of inflammatory cells were most prominent in DMN-3 group, and were decreased over time. Conclusion: The degree of hepatic uptake of LSA was inversely correlated with liver transaminase and degree of histologic liver injury in rat with acute hepatic injury.