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At least 235 records · Page 13
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

R2 relaxometry based MR imaging for estimation of liver iron content: A comparison between two methods

Purpose: To compare the reproducibility and accuracy of R2-relaxometry MRI for estimation of liver iron concentration (LIC) between in-house analysis and FDA-approved commercially available third party results. Methods: All MR studies were performed on a 1.5T scanner. Multi-echo spin-echo scans with a fixed TR and increasing TE values of 6 ms, 9 ms, 12 ms, 15 ms, and 18 ms (spaced at 3 ms intervals) were used. Post-processing of the images to calculate mean relaxivity, R2, included drawing of regions of interest to include the whole liver on mid-slice. The relationship between liver R2 values and estimated LIC calculated with in-house analysis and values reported by an external company (FerriScan{sup ®}, Resonance Health, Australia) were assessed with correlation coefficients and Bland–Altman difference plots. Continuous variables are presented as mean ± standard deviation. Significance was set at p value < 0.05. Results: 474 studies from 175 patients were included in the study (mean age 10.4 ± 4.2 years (range 1–18 years); 254 studies from girls, 220 studies from boys). LIC ranged from 0.6 to 43 mg/g dry tissue, covering a broad range from normal levels to extremely high iron levels. Linearity between proprietary and in-house methods was excellent across the observed range for R2 (31.5 to 334.8 s{sup −1}); showing a correlation coefficient of r = 0.87, p < 0.001. Bland–Altman R2 difference plot between the two methods shows a mean bias of + 21.5 s{sup −1} (range − 47.0 to + 90.0 s{sup −1} between two standard deviations). LIC reported by FerriScan{sup ®} compared with LIC estimated in-house with R2 as reported by FerriScan{sup ®} agreed strongly, (r = 1.0, p < 0.001). Conclusion: R2 relaxometry MR imaging for liver iron concentration estimation is reproducible between proprietary FDA-approved commercial software and in-house analysis methods.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

5-Fluorouracil induced liver toxicity in patients with colorectal cancer: role of computed tomography texture analysis as a potential biomarker

Purpose: To assess if CT texture analysis (TA) can serve as a biomarker of liver toxicity in patients with colorectal cancer treated with 5-fluorouracil (5-FU)-based chemotherapy. Methods: In this IRB-approved, HIPAA-compliant retrospective study, patients with colorectal cancer treated with 5-FU-based regimens during 2008–2010 were identified from institutional electronic database. Total 43 patients (23 women; mean age 56 years) with normal baseline liver function tests (LFTs), availability of baseline (pre-chemotherapy) and first follow-up CT (median 1.7 months, interquartile range (IQR) 1.5–2.5) performed during chemotherapy were included. Two single-slice ROI of right and left liver lobe were obtained on baseline and first follow-up CT for TA. Texture features [mean, entropy, kurtosis, skewness, mean of positive pixel, standard deviation (SD)] were extracted using a commercially available software (TexRAD; Feedback Medical Ltd, Cambridge, UK). Changes in texture parameters between baseline and follow-up CT were evaluated with Wilcoxon signed-rank test for patients with and without LFT elevation during chemotherapy. Results: Patients with LFT elevation (n = 34; 79%) showed significantly different mean, entropy, skewness, and SD (p values range 0.007–0.047) between baseline and first follow-up CT. No significant changes in features were observed in patients without LFT elevation (n = 9; 21%). In 19 patients (56%), first follow-up CT was performed before elevation of LFTs was observed. Conclusions: This proof-of-concept study shows that there are early changes in liver texture on first follow-up CT in patients with LFT elevation during 5-FU-based chemotherapy for colorectal cancer. In more than 50% of cases, these changes occur before LFT elevation becomes evident on blood tests.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2013

Radiofrequency Ablation of Liver Tumors in Combination with Local OK-432 Injection Prolongs Survival and Suppresses Distant Tumor Growth in the Rabbit Model with Intra- and Extrahepatic VX2 Tumors

Purpose: To evaluate survival and distant tumor growth after radiofrequency ablation (RFA) and local OK-432 injection at a single tumor site in a rabbit model with intra- and extrahepatic VX2 tumors and to examine the effect of this combination therapy, which we termed immuno-radiofrequency ablation (immunoRFA), on systemic antitumor immunity in a rechallenge test. Methods: Our institutional animal care committee approved all experiments. VX2 tumors were implanted to three sites: two in the liver and one in the left ear. Rabbits were randomized into four groups of seven to receive control, RFA alone, OK-432 alone, and immunoRFA treatments at a single liver tumor at 1 week after implantation. Untreated liver and ear tumor volumes were measured after the treatment. As the rechallenge test, tumors were reimplanted into the right ear of rabbits, which survived the 35 weeks and were followed up without additional treatment. Statistical significance was examined by log-rank test for survival and Student's t test for tumor volume. Results: Survival was significantly prolonged in the immunoRFA group compared to the other three groups (P < 0.05). Untreated liver and ear tumor sizes became significantly smaller after immunoRFA compared to controls (P < 0.05). In the rechallenge test, the reimplanted tumors regressed without further therapy compared to the ear tumors of the control group (P < 0.05). Conclusion: ImmunoRFA led to improved survival and suppression of distant untreated tumor growth. Decreases in size of the distant untreated tumors and reimplanted tumors suggested that systemic antitumor immunity was enhanced by immunoRFA.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

CT-guided Irreversible Electroporation in an Acute Porcine Liver Model: Effect of Previous Transarterial Iodized Oil Tissue Marking on Technical Parameters, 3D Computed Tomographic Rendering of the Electroporation Zone, and Histopathology

PurposeTo evaluate the effect of previous transarterial iodized oil tissue marking (ITM) on technical parameters, three-dimensional (3D) computed tomographic (CT) rendering of the electroporation zone, and histopathology after CT-guided irreversible electroporation (IRE) in an acute porcine liver model as a potential strategy to improve IRE performance.MethodsAfter Ethics Committee approval was obtained, in five landrace pigs, two IREs of the right and left liver (RL and LL) were performed under CT guidance with identical electroporation parameters. Before IRE, transarterial marking of the LL was performed with iodized oil. Nonenhanced and contrast-enhanced CT examinations followed. One hour after IRE, animals were killed and livers collected. Mean resulting voltage and amperage during IRE were assessed. For 3D CT rendering of the electroporation zone, parameters for size and shape were analyzed. Quantitative data were compared by the Mann–Whitney test. Histopathological differences were assessed.ResultsMean resulting voltage and amperage were 2,545.3 ± 66.0 V and 26.1 ± 1.8 A for RL, and 2,537.3 ± 69.0 V and 27.7 ± 1.8 A for LL without significant differences. Short axis, volume, and sphericity index were 16.5 ± 4.4 mm, 8.6 ± 3.2 cm{sup 3}, and 1.7 ± 0.3 for RL, and 18.2 ± 3.4 mm, 9.8 ± 3.8 cm{sup 3}, and 1.7 ± 0.3 for LL without significant differences. For RL and LL, the electroporation zone consisted of severely widened hepatic sinusoids containing erythrocytes and showed homogeneous apoptosis. For LL, iodized oil could be detected in the center and at the rim of the electroporation zone.ConclusionThere is no adverse effect of previous ITM on technical parameters, 3D CT rendering of the electroporation zone, and histopathology after CT-guided IRE of the liver.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2015

Is Antibiotic Prophylaxis for Percutaneous Radiofrequency Ablation (RFA) of Primary Liver Tumors Necessary? Results From a Single-Center Experience

PurposeThe purpose of this study was to evaluate need for antibiotic prophylaxis for radiofrequency ablation (RFA) of liver tumors in patients with no significant co-existing risk factors for infection.Materials and MethodsFrom January 2004 to September 2013, 83 patients underwent 123 percutaneous RFA procedures for total of 152 hepatocellular carcinoma (HCC) lesions. None of the patients had pre-existing biliary enteric anastomosis (BEA) or any biliary tract abnormality predisposing to ascending biliary infection or uncontrolled diabetes mellitus. No pre- or post-procedure antibiotic prophylaxis was provided for 121 procedures. Data for potential risk factors were reviewed retrospectively and analyzed for the frequency of infectious complications, including abscess formation.ResultsOne patient (1/121 (0.8 %) RFA sessions) developed a large segment 5 liver abscess/infected biloma communicating with the gallbladder 7 weeks after the procedure, successfully treated over 10 weeks with IV and PO antibiotic therapy and percutaneous catheter drainage. This patient did not receive any antibiotics prior to RFA. During the procedure, there was inadvertent placement of RFA probe tines into the gallbladder. No other infectious complications were documented.ConclusionThese data suggest that the routine use of prophylactic antibiotics for liver RFA is not necessary in majority of the patients undergoing liver ablation for HCC and could be limited to patients with high-risk factors such as the presence of BEA or other biliary abnormalities, uncontrolled diabetes mellitus, and large centrally located tumors in close proximity to central bile ducts. Larger randomized studies are needed to confirm this hypothesis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2016

Stereotactic Radiofrequency Ablation for Metastatic Melanoma to the Liver

PurposeTo evaluate the outcome of patients with melanoma liver metastasis treated with stereotactic radiofrequency ablation (SRFA).Material and MethodFollowing IRB approval, a retrospective evaluation of the treatment of 20 patients with 75 melanoma liver metastases was performed.ResultsA median number of 2 lesions (range 1–14) per patient with a median size of 1.7 cm (range 0.5–14.5 cm) were treated. 67 lesions were <3 cm (89.3 %) and 8 lesions were >3 cm (10.7 %). Per patient a median of 1 ablation session was performed (range: 1–4) totaling 34 sessions. There were no procedure-related deaths and all major complications (n = 3) could be easily treated by pleural drainages. The primary and secondary success rates were 89.3 and 93.3 %, respectively. The overall local recurrence rate was 13.3 %. Four of ten local recurrences were re-treated successfully by SRFA. During follow-up, 9/20 patients developed extrahepatic metastatic disease and 10/20 had liver recurrence at any location. The median OS from the date of SRFA was 19.3 months, with an OS of 64, 41, and 17 % at 1, 3, and 5 years, with no significant difference for patients with cutaneous and ocular melanoma. The median DFS after SRFA for all 20 patients was 9.5 months, with 37, 9, and 0 % at 1, 3, and 5 years.ConclusionsDue to the high local curative potential and the promising long-term survival rates associated with minimal morbidity and mortality, radiofrequency ablation seems to be an attractive alternative to resection in patients with melanoma liver metastases.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Doxorubicin-Loaded 70–150 μm Microspheres for Liver-Dominant Metastatic Breast Cancer: Results and Outcomes of a Pilot Study

PurposePatients with breast cancer liver metastasis have a poor prognosis. Local therapy for liver metastasis increases survival. The purpose of this pilot prospective study was to evaluate the efficacy and safety of doxorubicin drug-eluting beads chemoembolization for liver-dominant breast cancer metastasis (LdBM) refractory to chemotherapy.Materials and MethodsAll patients with LdBM refractory to of two or more lines of systemic chemotherapy were screened. Two chemoembolizations at 1-month intervals were scheduled for each patient. Tumor responses were evaluated by MRI every 3 months until progression or death. Adverse events were recorded according to the Common Terminology Criteria for Adverse Events (CTCAE version 4.02) 1 month after each chemoembolization. All patients were free from systemic treatment until progression. Patients with hormone-positive receptors and/or HER-positive disease status continued their targeted therapy.ResultsOut of 23 patients enrolled (mean age: 57.5 ± 11.5 years), 17 completed two chemoembolizations and six underwent only one because of severe adverse events. At 3-month follow-up, the disease control rate was 83 %. The median progression-free survival from the first chemoembolization was 8 months, and the median overall survival was 17 months. Nineteen patients remained free from any systemic chemotherapy for a mean of 209 ± 92 days until progression. Eight grade 3 (asthenia n = 3, anemia n = 2, thrombocythemia n = 2, liver toxicity n = 1) (Rev 1 Comment 1) occurred after the first procedure. No patient died directly due to the procedure.ConclusionWhile chemoembolization with doxorubicin eluding beads for refractory LdBM leads to an 83 % disease control rate, it also causes severe side effects that need to be adequately managed.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Percutaneous Thermal Ablation with Ultrasound Guidance. Fusion Imaging Guidance to Improve Conspicuity of Liver Metastasis

PurposeTo assess whether fusion imaging-guided percutaneous microwave ablation (MWA) can improve visibility and targeting of liver metastasis that were deemed inconspicuous on ultrasound (US).Materials and MethodsMWA of liver metastasis not judged conspicuous enough on US was performed under CT/US fusion imaging guidance. The conspicuity before and after the fusion imaging was graded on a five-point scale, and significance was assessed by Wilcoxon test. Technical success, procedure time, and procedure-related complications were evaluated.ResultsA total of 35 patients with 40 liver metastases (mean size 1.3 ± 0.4 cm) were enrolled. Image fusion improved conspicuity sufficiently to allow fusion-targeted MWA in 33 patients. The time required for image fusion processing and tumors’ identification averaged 10 ± 2.1 min (range 5–14). Initial conspicuity on US by inclusion criteria was 1.2 ± 0.4 (range 0–2), while conspicuity after localization on fusion imaging was 3.5 ± 1 (range 1–5, p < 0.001). Technical success rate was 83% (33/40) in intention-to-treat analysis and 100% in analysis of treated tumors. There were no major procedure-related complications.ConclusionsFusion imaging broadens the scope of US-guided MWA to metastasis lacking adequate conspicuity on conventional US. Fusion imaging is an effective tool to increase the conspicuity of liver metastases that were initially deemed non visualizable on conventional US imaging.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2017

Stabilization Improves Theranostic Properties of Lipiodol{sup ®}-Based Emulsion During Liver Trans-arterial Chemo-embolization in a VX2 Rabbit Model

PurposeTo demonstrate that stability is a crucial parameter for theranostic properties of Lipiodol{sup ®}-based emulsions during liver trans-arterial chemo-embolization.Materials and MethodsWe compared the theranostic properties of two emulsions made of Lipiodol{sup ®} and doxorubicin in two successive animal experiments (One VX2 tumour implanted in the left liver lobe of 30 rabbits). Emulsion-1 reproduced one of the most common way of preparation (ratio of oil/water: 1/1), and emulsion-2 was designed to obtain a water-in-oil emulsion with enhanced stability (ratio of oil/water: 3/1, plus an emulsifier). The first animal experiment compared the tumour selectivity of the two emulsions: seven rabbits received left hepatic arterial infusion (HAI) of emulsion-1 and eight received HAI of emulsion-2. 3D-CBCT acquisitions were acquired after HAI of every 0.1 mL to measure the densities’ ratios between the tumours and the left liver lobes. The second animal experiment compared the plasmatic and tumour doxorubicin concentrations after HAI of 1.5 mg of doxorubicin administered either alone (n = 3) or in emulsion-1 (n = 6) or in emulsion-2 (n = 6).ResultsEmulsion-2 resulted in densities’ ratios between the tumours and the left liver lobes that were significantly higher compared to emulsion-1 (up to 0.4 mL infused). Plasmatic doxorubicin concentrations (at 5 min) were significantly lower after HAI of emulsion-2 (19.0 μg/L) than emulsion-1 (275.3 μg/L, p < 0.01) and doxorubicin alone (412.0 μg/L, p < 0.001), and tumour doxorubicin concentration (day-1) was significantly higher after HAI of emulsion-2 (20,957 ng/g) than in emulsion-1 (8093 ng/g, p < 0.05) and doxorubicin alone (2221 ng/g, p < 0.01).ConclusionStabilization of doxorubicin in a water-in-oil Lipiodol{sup ®}-based emulsion results in better theranostic properties.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Outcomes After Transarterial Embolization of Neuroendocrine Tumor Liver Metastases Using Spherical Particles of Different Sizes

Purpose: To evaluate initial response and overall survival of neuroendocrine tumor (NET) liver metastases initially treated with transarterial embolization (TAE) using spherical particles of different sizes. Methods: A single-institution retrospective review was performed of 160 patients with NET liver metastases initially treated with TAE using < 100 µm (n = 77) or only ≥ 100 µm (n = 83) spherical particles. For each patient, we evaluated: initial response by mRECIST, time to progression, overall survival, complications, primary site, tumor grade and degree of differentiation, volume of liver disease, extrahepatic disease, NET-related symptoms, comorbidities, Child–Pugh score, performance status, lobar versus selective embolization, and arteriovenous shunting. Results: Initial response was higher for TAE using particles < 100 versus TAE using only particles ≥ 100 μm (64 vs 42%, p = 0.007). Multivariate logistic regression showed that use of particles < 100 μm and liver < 50% replaced with tumor were independent predictors of a better initial response rate. There was no difference in major or minor complications between the two particle size groups. Median overall survival after TAE was 55 months for well- to moderately differentiated NET and 13 months for poorly differentiated or undifferentiated NET. There was no significant difference in survival between TAE patients treated with < 100 versus only ≥ 100-μm particles. Conclusion: NET patients treated with TAE using particles < 100 μm had better initial response, but the same overall survival, compared to TAE using only particles ≥ 100 μm.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

Feasibility of Percutaneous Intrahepatic Split by Microwave Ablation (PISA) After Portal Vein Embolization for Hypertrophy of Future Liver Remnant: The Radiological Stage-1 ALPPS

PurposeTo assess the feasibility of radiological stage-1 ALPPS, associating liver partition and portal vein ligation for staged hepatectomy, by combining portal vein embolization (PVE) with percutaneous intrahepatic split by ablation (PISA).Materials and MethodsThree patients (mean age 65.0 ± 7.3 years) underwent PVE and PISA. PISA was performed 21 days after PVE by microwave ablation to create a continuous intrahepatic cutting plane. Abdominal CT examinations were performed before and after PVE and PISA. The future liver remnant (FLR) volume was calculated by semiautomatic segmentation, and increase was reported as a percentage of the pre-procedural volume. The FLR/body weight (FLR/BW) ratio was calculated; a ratio greater than 0.8% was considered sufficient for guaranteeing adequate liver function after surgery. The liver function before and after PISA was also evaluated by 99mTc-mebrofenin hepatobiliary scintigraphy. Patients’ laboratory tests, performance status, ability to walk were assessed before and after PVE and PISA procedures.ResultsNo procedure-related complications were recorded. The FLR volume increase in each patient was 42.0, 33.1 and 30.4% within 21 days of PVE and 109.3, 68.1 and 71.7% within 10 days after PISA. The FLR/BW ratios were 0.76, 0.66, 0.63% and 1.13, 0.83, 0.83% after PVE and PISA procedures, respectively. Two patients underwent successful right hepatectomy; in one patient, despite 1.13% FLR/BW, surgery was not performed because of the absolute rejection of blood transfusion due to the patient’s religious convictions.ConclusionRadiological stage-1 ALPPS is a feasible, minimally invasive option to be further investigated to become an effective alternative to surgical stage-1 ALPPS.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2019

Utility of the Virtual Liver Parenchymal Perfusion Area Using a Commercially Available Workstation in Transarterial Chemoembolization for Hepatocellular Carcinoma

Purpose: To evaluate the accuracy of the virtual liver parenchymal perfusion area using a commercially available workstation and liver analysis software in conventional transarterial chemoembolization (cTACE) for hepatocellular carcinoma (HCC). Materials and Methods: This method was retrospectively applied to 29 treated HCCs in 23 patients. The virtual embolic area (VEA) was estimated based on cone beam computed tomography during hepatic arteriography using a commercially available workstation and liver analysis software by two observer groups (group A: experts; group B: semi-experts). The real embolic area (REA) was defined as the area where iodized oil accumulated on computed tomography at 1 week after cTACE. The REA was estimated by each of the two groups, and the mean REA between the groups (mREA) was used as a standard reference. Agreement of volume and cross-sectional area in three orthogonal planes between the VEA and mREA were analyzed using intraclass correlation coefficients (ICCs) and Bland–Altman plots. Results: The ICCs for volume between VEA and mREA were 0.97 and 0.88 for groups A and B, respectively, and those for cross-sectional area were 0.94 and 0.88 for the axial plane, 0.95 and 0.83 for the coronal plane, and 0.87 and 0.74 for the sagittal plane, respectively. Thus, the overall agreement was excellent, except for the sagittal imaging plane in group B. Conclusion: This method using a commercially available workstation and liver analysis software can be useful for estimating the embolic area in cTACE.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2018

9-cis-retinoic acid elevates MRP3 expression by inhibiting sumoylation of RXRα to alleviate cholestatic liver injury

Highlights: • 9-cis-retinoic acid alleviates BDL induced liver injury and may be a new strategy to relief cholestasis. • 9-cis-retinoic acid elevates MRP3 expression by the inhibition of RXRα sumoylation in cholestatic disorders. • Inhibition of RXRα sumoylation promotes it cytoplasmic distribution and weakens the interaction of RXRα and RARα. Vitamin A and its metabolites has been found to be protective against cholestatic liver injury, but the exact underlying mechanisms involved in cholestatic liver injury remain unclear. The objective of this study was to determine the function and mechanisms of 9-cis-retinoic acid, the metabolite of vitamin A, in cholestatic liver injury.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The circulating immunoglobulins negatively impact on the parasite clearance in the liver of Leishmania donovani-infected mice via dampening ROS activity

Highlights: • Mice with the absence of circulating immunoglobulins are resistant to Leishmania donovani infection. • The clearance of parasites in liver of these mice occurs from the early stage of infection. • This rapid clearance is independent of interferon gamma. • Reactive oxygen species pathway is involved in this rapid clearance. • Circulating immunoglobulins dampens reactive oxygen species pathway in the liver of Leishmania donovani-infected mice. Visceral leishmaniasis, the most severe form of leishmaniasis, is caused by Leishmania donovani and L. infantum. Immunity to Leishmania infection has been shown to depend on the development of Th1 cells; however, the roles of B cells and antibodies during infection remain unclear. In the present study, we showed that AID and μs double-deficient mice (DKO), which have B cells but not circulating immunoglobulins (cIgs), became resistant to L. donovani infection, whereas μs or AID single-deficient mice did not. This resistance in DKO mice occurred in the liver from an early stage of the infection. The depletion of IFN-γ did not affect the rapid reduction of parasite burden, whereas NADPH oxidases was up-regulated in the livers of infected DKO mice. The inhibition of the reactive oxygen species pathway in vivo by apocynin, a NADPH oxidase inhibitor, resulted in a significant increase in the parasite burden in DKO mice. These results indicate that a circulating Ig deficiency induces a protective response against L. donovani infection by elevating IFN-γ-independent NADPH oxidase activity, and also that cIgs play a regulatory role in controlling L. donovani infection in mice.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Quantifying Rigid and Nonrigid Motion of Liver Tumors During Stereotactic Body Radiation Therapy

Purpose: To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT). Methods and Materials: Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections. Results: The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections. Conclusions: Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator–based liver SBRT.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Is Diaphragm Motion a Good Surrogate for Liver Tumor Motion?

Purpose: To evaluate the relationship between liver tumor motion and diaphragm motion. Methods and Materials: Fourteen patients with hepatocellular carcinoma (10 of 14) or liver metastases (4 of 14) undergoing radiation therapy were included in this study. All patients underwent single-slice cine–magnetic resonance imaging simulations across the center of the tumor in 3 orthogonal planes. Tumor and diaphragm motion trajectories in the superior–inferior (SI), anterior–posterior (AP), and medial–lateral (ML) directions were obtained using an in-house-developed normalized cross-correlation–based tracking technique. Agreement between the tumor and diaphragm motion was assessed by calculating phase difference percentage, intraclass correlation coefficient, and Bland-Altman analysis (Diff). The distance between the tumor and tracked diaphragm area was analyzed to understand its impact on the correlation between the 2 motions. Results: Of all patients, the mean (±standard deviation) phase difference percentage values were 7.1% ± 1.1%, 4.5% ± 0.5%, and 17.5% ± 4.5% in the SI, AP, and ML directions, respectively. The mean intraclass correlation coefficient values were 0.98 ± 0.02, 0.97 ± 0.02, and 0.08 ± 0.06 in the SI, AP, and ML directions, respectively. The mean Diff values were 2.8 ± 1.4 mm, 2.4 ± 1.1 mm, and 2.2 ± 0.5 mm in the SI, AP, and ML directions, respectively. Tumor and diaphragm motions had high concordance when the distance between the tumor and tracked diaphragm area was small. Conclusions: This study showed that liver tumor motion had good correlation with diaphragm motion in the SI and AP directions, indicating diaphragm motion in the SI and AP directions could potentially be used as a reliable surrogate for liver tumor motion.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2014

Autophagy in drug-induced liver toxicity

Liver injury resulting from exposure to drugs and chemicals is a major health problem. Autophagy is an important factor in a wide range of diseases, such as cancer, liver disease, muscular disorder, neurodegeneration, pathogen infection, and aging, and emerging evidence indicates that autophagy makes a substantial contribution to the pathogenesis of drug- and chemical-induced liver toxicity. In this review, we summarize current knowledge on autophagy triggered by toxicants/toxins, the protective role of autophagy in liver toxicity, and the underlying molecular mechanisms. We also highlight experimental approaches for studying autophagy.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2014

A technique using {sup 99m}Tc-mebrofenin SPECT for radiotherapy treatment planning for liver cancers or metastases

Radiotherapy or stereotactic body radiosurgery (SBRT) requires a sufficient functional liver volume to tolerate the treatment. The current study extended the work of de Graaf et al. (2010) [3] on the use of {sup 99m}Tc-mebrofenin imaging for presurgery planning to radiotherapy planning for liver cancer or metastases. Patient was immobilized and imaged in an identical position on a single-photon emission computed tomography/computed tomography (SPECT-CT) system and a radiotherapy simulation CT system. {sup 99m}Tc-mebrofenin SPECT was registered to the planning CT through image registration of noncontrast CT from SPECT-CT system to the radiotherapy planning CT. The voxels with higher uptake of {sup 99m}Tc-mebrofenin were transferred to the planning CT as an avoidance structure in optimizing a 2-arc RapidArc plan for SBRT delivery. Excellent dose coverage to the target and sparing of the healthy remnant liver volume was achieved. This report illustrated a procedure for the use of {sup 99m}Tc-mebrofenin SPECT for optimizing radiotherapy for liver cancers and metastases.

61 RADIATION PROTECTION AND DOSIMETRY↗