Decrease In Contrast Enhancement Research Articles

Targeting myeloperoxidase to stabilize unruptured aneurysm: an imaging-guided approach

Inflammation plays a key role in pathogenesis and rupture of aneurysms. Non-invasively and dynamically monitoring aneurysm inflammation is critical. This study evaluated myeloperoxidase (MPO) as an imaging biomarker and therapeutic target for aneurysm inflammation using an elastase-induced rabbit model treated with or without 4-aminobenzoic acid hydrazide (ABAH), an irreversible inhibitor of MPO. Myeloperoxidase-sensitive magnetic resonance imaging (MRI) using Mn-TyrEDTA, a peroxidase activity-dependent contrast agent, revealed weak contrast enhancement in contralateral arteries and decreased contrast enhancement in aneurysm walls with ABAH treatment, indicating MPO activity decreased and inflammation mitigated. This was supported by reduced immune cell infiltration, matrix metalloproteinases (MMP-2 and − 9) activity, ROS production and arterial wall destruction on histology. Finally, the aneurysm expansion rate remained < 50% throughout the study in the ABAH(+) group, but increased gradually in the ABAH(-) group. Our results suggest that inhibition of MPO attenuated inflammation and expansion of experimental aneurysm and MPO-sensitive MRI showed promise as a noninvasive tool for monitoring aneurysm inflammation.

Primary renal triple expressor DLBCL treated with chemotherapy under continuous hemodialysis and filtration support

A 69-year-old woman was previously treated with antibiotics for suspected pyelonephritis due to fever but showed limited improvement. Contrast-enhanced CT revealed heterogeneous areas of decreased contrast enhancement in both kidneys, along with an elevated soluble level of the IL-2 receptor (5,090 U/ml), and thus the patient was referred to our department for further evaluation. A percutaneous renal biopsy performed due to suspected malignant lymphoma confirmed lymphoma cell infiltration into the renal interstitium. Immunohistochemical staining was positive for MYC/BCL2/BCL6, leading to the diagnosis of stage IVB primary renal triple expressor diffuse large B cell lymphoma (DLBCL). Due to acute kidney injury, continuous hemodiafiltration (CHDF) was initiated, followed by rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy. The patient's renal function improved rapidly, and complete response was achieved after six cycles of R-CHOP. Although DLBCL is a common lymphoma, the primary renal subtype is extremely rare and poses both diagnostic and therapeutic challenges. This case highlights the potential clinical implications of combining CHDF with chemotherapy to achieve complete response despite an initial poor prognosis based on the patient's overall clinical condition and pathology.

Pentoxifylline and Vitamin E Can Restrict Radiation Necrosis via Vascular Pathways, Experimental Study in an Animal Model

Radiation necrosis (RN) is a long-term side effect of Gamma Knife stereotactic radiosurgery that may require surgical intervention. Pentoxifylline and vitamin E have previously been shown to be effective in the treatment of RN in the published literature, but there are no data on the prophylactic use of these molecules or, more importantly, whether prophylaxis is required. The iatrogenic RN model included 50 Sprague-Dawley rats of both sexes. There were 7 treatment subgroups established. Gamma-Plan 8.32 was used to plan after magnetic resonance scans were performed in a specially designed frame. The injection doses used in the treatment groups were vitamin E (30mg/kg/day in a single dose) and pentoxifylline (50mg/kg/day in 2 doses). Control magnetic resonance scans were performed at the end of a 16-week treatment, and the subjects were decapitated for pathological evaluations. The intensity of hypoxia - inducible factor 1α immunoreactivity is statistically significantly lower in the therapeutic vitamin E, prophylactic pentoxifylline and vitamin E, and therapeutic pentoxifylline and vitamin E groups than in the other groups. Similarly, the intensity of vascular endothelial growth factor immunoreactivity was reduced in the therapeutic vitamin E and prophylactic pentoxifylline and vitamin E treatment modality groups.When compared with other groups, the therapeutic pentoxifylline group had significantly fewer vascular endothelial growth factor-immunoreactive cells in the perinecrotic area, with an accompanying decreased contrast enhancement pattern. Both vitamin E and pentoxifylline are effective for the treatment and/or restriction of RN, either alone or in combination. The use of these molecules as a preventive measure did not outperform the therapeutic treatment.

Efficacy of Targeted ECO/miR-200c Nanoparticles for Modulating Tumor Microenvironment and Treating Triple Negative Breast Cancer as Non-invasively Monitored by MR Molecular Imaging.

To investigate the effectiveness of targeted ECO/miR-200c in modulating tumor microenvironment and treating triple negative breast cancer (TNBC) using non-invasive magnetic resonance molecular imaging (MRMI) of extradomain B fibronectin (EDB-FN) with a targeted MRI contrast agent. MDA-MB-231 and Hs578T TNBC cells were transfected with RGD-PEG-ECO/miR-200c. Invasive and migratory potential was evaluated using transwell, scratch wound, and spheroid formation assays. Athymic nude mice bearing orthotopic MDA-MB-231 and Hs578T xenografts were treated with weekly i.v. injection of RGD-PEG-ECO/miR-200c nanoparticles at 1.0 mg/kg/week RNA for 6weeks. MRMI of EDB-FN was performed using a targeted contrast agent MT218 [ZD2-N3-Gd(DO3A)] on a 3T MRS 3000 scanner. T1-weighted images were acquired following intravenous injection of MT218 at dose of 0.1mmol/kg using a fast spin echo axial sequence with respiratory gating. Systemic administration of RGD-PEG-ECO/miR-200c nanoparticles in mice bearing orthotopic TNBC xenografts significantly suppressed tumor progression without toxic side-effects. MRMI with MT218 revealed that the treatment significantly suppressed tumor proliferation as compared to the control. MRMI also showed that the miR-200c treatment altered tumor microenvironment by reducing EDB-FN expression, as evidenced by decreased contrast enhancement in both MDA-MB-231 and Hs578T tumors. The reduction of EDB-FN was confirmed by immunohistochemistry. Targeted delivery of miR-200c with RGD-PEG-ECO/miR-200c nanoparticles effectively modulates tumor microenvironment and suppresses TNBC proliferation in animal models. MRMI of tumor EDB-FN expression is effective to non-invasively monitor tumor response and therapeutic efficacy of RGD-PEG-ECO/miR-200c nanoparticles in TNBC.

Lipid bubbles combined with low-intensity ultrasound enhance the intratumoral accumulation and antitumor effect of pegylated liposomal doxorubicin in vivo

Pegylated liposomal doxorubicin (PLD) is a representative nanomedicine that has improved tumor selectivity and safety profile. However, the therapeutic superiority of PLD over conventional doxorubicin has been reported to be insignificant in clinical medicine. Combination treatment with microbubbles and ultrasound (US) is a promising strategy for enhancing the antitumor effects of chemotherapeutics by improving drug delivery. Recently, several preclinical studies have shown the drug delivery potential of lipid bubbles (LBs), newly developed monolayer microbubbles, in combination with low-intensity US (LIUS). This study aimed to elucidate whether the combined use of LBs and LIUS enhanced the intratumoral accumulation and antitumor effect of PLD in syngeneic mouse tumor models. Contrast-enhanced US imaging using LBs showed a significant decrease in contrast enhancement after LIUS, indicating that LIUS exposure induced the destruction of LBs in the tumor tissue. A quantitative evaluation revealed that the combined use of LBs and LIUS improved the intratumoral accumulation of PLD. Furthermore, tumor growth was inhibited by combined treatment with PLD, LBs, and LIUS. Therefore, the combined use of LBs and LIUS enhanced the antitumor effect of PLD by increasing its accumulation in the tumor tissue. In conclusion, the present study provides important evidence that the combination of LBs and LIUS is an effective method for enhancing the intratumoral delivery and antitumor effect of PLD in vivo.

Evaluation of metronomic chemotherapy response using diffusion and dynamic contrast-enhanced MRI.

To investigate the feasibility of using diffusion MRI (dMRI) and dynamic contrast-enhanced (DCE) MRI to evaluate the treatment response of metronomic chemotherapy (MCT) in the 4T1 mammary tumor model of locally advanced breast cancer. Twelve Balb/c mice with metastatic breast cancer were divided into treated and untreated (control) groups. The treated group (n = 6) received five treatments of anti-metabolite agent 5-Fluorouracil (5FU) in the span of two weeks. dMRI and DCE-MRI were acquired for both treated and control groups before and after MCT. Immunohistochemically staining and measurements were performed after the post-MRI measurements for comparison. The control mice had significantly (p<0.005) larger tumors than the MCT treated mice. The DCE-MRI analysis showed a decrease in contrast enhancement for the control group, whereas the MCT mice had a more stable enhancement between the pre-chemo and post-chemo time points. This confirms the antiangiogenic effects of 5FU treatment. Comparing amplitude of enhancement revealed a significantly (p<0.05) higher enhancement in the MCT tumors than in the controls. Moreover, the MCT uptake rate was significantly (p<0.001) slower than the controls. dMRI analysis showed the MCT ADC values were significantly larger than the control group at the post-scan time point. dMRI and DCE-MRI can be used as potential biomarkers for assessing the treatment response of MCT. The MRI and pathology observations suggested that in addition to the cytotoxic effect of cell kills, the MCT with a cytotoxic drug, 5FU, induced changes in the tumor vasculature similar to the anti-angiogenic effect.

Decreased contrast enhancement on high-resolution vessel wall imaging of unruptured intracranial aneurysms in patients taking aspirin.

Inflammation plays an integral role in the formation, growth, and progression to rupture of unruptured intracranial aneurysms (UIAs). Animal and human studies have suggested that, due to its antiinflammatory effect, aspirin (ASA) may decrease the risks of growth and rupture of UIAs. High-resolution vessel wall imaging (HR-VWI) has emerged as a noninvasive method to assess vessel wall inflammation and UIA instability. To the authors' knowledge, to date no studies have found a significant correlation between patient use of ASA and contrast enhancement of UIAs on HR-VWI. The University of Iowa HR-VWI Project database was analyzed. This database is a compilation of data on patients with UIAs who prospectively underwent HR-VWI on a 3T Siemens MRI scanner. The presence of aneurysmal wall enhancement was objectively defined using the aneurysm-to-pituitary stalk contrast ratio (CRstalk). This ratio was calculated by measuring the maximal signal intensity in the aneurysmal wall and the pituitary stalk on postcontrast T1-weighted images. Data on aneurysm size, morphology, and location and patient demographics and comorbidities were collected. Use of ASA was defined as daily intake of ≥ 81 mg during the previous 6 months or longer. Univariate and multivariate logistic regression analyses were performed to determine factors independently associated with increased contrast enhancement of UIAs on HR-VWI. In total, 74 patients harboring 96 UIAs were included in the study. The mean patient age was 64.7 ± 12.4 years, and 60 patients (81%) were women. Multivariate analysis showed that age (OR 1.12, 95% CI 1.05-1.19), aneurysm size ≥ 7 mm (OR 21.3, 95% CI 4.88-92.8), and location in the anterior communicating, posterior communicating, and basilar arteries (OR 10.7, 95% CI 2.45-46.5) were significantly associated with increased wall enhancement on HR-VWI. On the other hand, use of ASA was significantly associated with decreased aneurysmal wall enhancement on HR-VWI (OR 0.22, 95% CI 0.06-0.83, p = 0.026). The study results establish a correlation between use of ASA daily for ≥ 6 months and significant decreases in wall enhancement of UIAs on HR-VWI. The findings also demonstrate that detection of wall enhancement using HR-MRI may be a valuable noninvasive method for assessing aneurysmal wall inflammation and UIA instability.

P14.07 Complete response under treatment with proton therapy followed by chemotherapy together with Tumor Treating Fields in a biopsied IDH wildtype glioblastoma patient

Abstract BACKGROUND Proton therapy is able to apply high radiation doses to the tumor while sparing healthy tissues by reducing integral dose. Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) and intermediate frequency (100–300 kHz) alternating electric fields that demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma (ndGBM). Especially in ndGBM IDH wildtype with unmethylated MGMT promotor therapeutic options are restricted. Here, we report on a patient with biopsied ndGBM IDH wildtype with complete radiological response. MATERIAL AND METHODS Brain MRI demonstrated an occlusive hydrocephalus and a ring enhancing lesion in the right posterior thalamus in a 42 year old male. Endoscopic third ventriculostomy and stereotactic biopsy of the lesion were performed. Histopathological examination resulted in the diagnosis of a glioblastoma (WHO grade IV), IDH 1 wildtype (R132), IDH 2 wildtype (R172), HIST1H3B/C wildtype, TERT wildtype (C228 and C250), BRAF wildtype, and unmethylated MGMT promotor. In view of the tumor site, resection was not feasible. Consequently, the patient received definitive chemoradiation with TMZ to a total dose of 60Gy incl. proton boost of 5x2 GyRBE. TTFields therapy in combination with TMZ was initiated 4 weeks after completion of chemoradiation, TMZ maintenance was completed per protocol after 6 cycles. TTFields therapy was continued for more than 13 month and to-date the patient is still on therapy. RESULTS Current follow up time is 20 months after initial diagnosis with the patient showing a radiological complete response. The first MRI following chemoradiation with TMZ and protons (showed pseudoprogression. After 3 months, the MRI again showed slightly increasing contrast enhancement. However, no clinical symptoms of tumor progression were present. The TTFields usage (compliance) rate, i.e. the rate per time the patient is applying the therapy, of the patient was 86 %. This was well above the independent prognostic threshold of 75 % and supports the feasibility of this approach. A further MRI after 8 weeks showed a stable disease. In a MRI 4 months later, partial response with decreased contrast enhancement plus perfusion restriction in the tumor area was observed. Another MRI after 3 months showed a complete response without perfusion signal in the tumor area. In the clinical examination the patient had no neurological deficits and to-date the patient is still stable CONCLUSION Complete response was observed following combination treatment of chemoradiation with TMZ including proton boost, TMZ maintenance and TTFields in a patient with pathologically confirmed GBM IDH wildtype. To our knowledge, this is the first report on a ndGBM patient receiving proton therapy followed by TTFields therapy.

Quantification accuracy for dynamic contrast enhanced (DCE) CT imaging: phantom and quality assurance framework

PurposeStandardization and protocol optimization is essential for quantification of Dynamic Contrast Enhanced CT as an imaging biomarker. Currently, no commercially available quality assurance (QA) phantoms can provide for testing a complete set of imaging parameters pertaining to routine quality control for contrast-enhanced (CE) CT, as well as spatiotemporal accuracy. The purpose of this work was, therefore: (a) developing a solid calibration phantom for routine CE CT quality assurance; (b) investigating the sensitivity of CECT to organ motion, and (c) characterizing a volumetric CT scanner for CECT. MethodsCECT calibration phantom consisting of an acrylic uniform cylinder containing multiple capsules of varying diameters and orientations was designed and built. The capsules contain different solid density materials mimicking iodine contrast enhancement. Sensitivity and accuracy of CECT measurements on all capsules was performed using a 320-slice CT scanner for a range of scan parameters both with and without phantom motion along the transaxial axis of the scanner. ResultsRoutine commissioning tests such as uniformity, spatial resolution and image noise were successfully determined using the CECT phantom. Partial volume effect and motion blurring both contribute to a general decrease in contrast enhancement and this was further dependent on capsule orientation (least pronounced for the transaxial orientation). Scanning with a rotation time of less than 0.5 s, the effect of blurring is less than 3% for all orientations and phantom speeds. ConclusionA new robust contrast calibration phantom was developed and used to evaluate the performance of a 320-slice volumetric CT scanner for DCE-CT.

Abstract 361: Multifocal Vascular Disorders Due to the Uncommon Anti-phosholipid Antibody Syndrome

Purpose: We report three cases with uncommon anti-phosholipid antibody syndrome. The difficulty in diagnosing as well as treatment procedures for multifocal vascular disorders is discussed. Patients and Methods: All patients were examined and were initially treated for digestive disorders. Patient 1, 84-year-old woman, with gastrointestinal bleeding Patient 2, 76-year-old man, with sudden onset of upper abdominal pain Patient 3, 54-year-old man, with nausea and vomiting, liver dysfunctionClinical manifestation was superior mesenteric artery (SMA) thrombosis in the patient 1 and 2, and portal vein thrombosis in the patient 3. Serial CT scans were examined on 64 multidetector-row CT; Hitachi and GE, with bolus injection of contrast media for CT angiography. Abdominal angiography and coronary angiography with endovascular intervention performed on were performed on Allura; Philips. Results: CTA of for patient 1 and 2 showed decreased contrast enhancement of SMA and SMV enhancement. The intestinal enhancement was poor in patient 1 and well preserved in patient 2. A week later, patient 1 died suddenly due to multiple organ failure. Although the symptom improved in patient 2, the follow-up CT revealed the enlargement ofSMA thrombosis. The aspiration and the dissolution of SMA thrombosis were performed and resulted in complete recanalization. Then he felt chest oppression and 75% stenosis of RCA #4, followed by complete spastic occlusion on Acetylcholine loading on the coronary angiography, which recovered perfectly with intracoronary nitroglycerin administration.He discharged our hospital with health, while he developed cerebellar infarction. On patient 3, to resolve portal hypertension, balloon-occluded retrograde transvenous obliteration and splenic arterial embolization were successfully performed. Discussion and Conclusions: Acute deterioration encountered in patient 1, the progressive SMA thrombosis with coronary disease and subsequent cerebellar occlusion seen in patient 2, and portal vein thrombosis and portal hypertension without chronic hepatitis, cirrhosis or alcoholic liver damage in the patient 3 were seemed to be unusual. To discover underlining disorders such as uncommon anti-phosholipid antibody syndrome is important to prevent serious vascular diseases in sequence.

Unusual Magnetic Resonance Imaging Findings of a Glioblastoma Arising During Treatment with Lenvatinib for Thyroid Cancer

Glioblastoma (GBM) is a lesion radiologically characterized by magnetic resonance imaging findings, such as ring enhancement with extensive perifocal edema and a butterfly appearance extending into the bilateral lobes. However, these characteristic findings could be changed by antiangiogenic therapy, with decreased contrast enhancement and improved perifocal edema. Herein, we report a case of GBM that arose during treatment with a tyrosine kinase inhibitor for another cancer. A 57-year-old man presented with seizures. Until the seizure onset, he had been treated with the multireceptor tyrosine kinase inhibitor lenvatinib for 4 years for thyroid cancer and its metastasis to the thoracic vertebral body. Magnetic resonance imaging revealed a slightly high intensity lesion in the left frontal base area on T2-weighted or fluid-attenuated inversion recovery images, and the lesion showed only faint enhancement on T1-weighted images after gadolinium administration. Total resection was performed and the histopathologic diagnosis was GBM. However, grade IV histology was observed in only a limited area, and most of the specimen showed lower grade histology with moderate vascularization that lacked microvascular proliferation. Lenvatinib, which is antiangiogenic, might have affected the radiologic characteristics, as well as the pathology of the tumor. Brain tumors arising during treatment with receptor tyrosine kinases for other cancers could show atypical imaging findings.

Abstract 3730: Early metabolic response to tumor-treating fields in patients with recurrent glioblastoma

Abstract PURPOSE. Tumor-Treating Fields (TTFields) is an FDA-approved treatment approach for patients with both newly-diagnosed and recurrent glioblastoma. The main purpose of the present study was to explore if amino acid positron emission tomography (PET) is able to detect an early, objective metabolic tumor response during the first months of TTFields therapy. METHODS. Patients with MRI signs of recurrent glioblastoma eligible for TTFields along with maintenance temozolomide were recruited for PET scanning with alpha[C-11]-methyl-L-tryptophan (AMT) at baseline (before start of TTFields application) and up to 3 months later. Serial MRIs were also performed in 1-2 months intervals. AMT accumulation in the MRI-detected tumor mass was measured by standardized uptake values (SUVs), and PET-based tumor volumes were also calculated. Interval changes of these PET variables were compared to changes in areas of MRI enhancement. RESULTS. Out of 7 recruited patients, 5 showed appropriate compliance (&amp;gt;75%) with the device and underwent follow-up PET. Four of the 5 patients showed a clear metabolic response during TTF treatment on PET imaging. Two patients, who received TTFields treatment only (in addition to maintenance temozolomide), showed 25% and 100% decrease of PET-based tumor volumes, respectively. MRI was stable (patient #1) or showed increasing contrast enhancement (#2) during the same period. In this latter patient, TTFields was continued with bevacizumab treatment, leading to decreased contrast enhancement and further decrease of AMT uptake on a second follow-up PET. In two other patients (#3 and #4), TTFields were combined with bevacizumab rescue treatment. Patient #3 showed a markedly decreased tumoral AMT uptake and metabolic volume along with stable MRI enhancement. Patient #4 showed interval decrease of tryptophan PET uptake 2 months after initiation of TTFields therapy. Finally, patient #5 showed an interval expansion of the PET-based tumor volume along with MRI progression during a 2-month follow-up despite TTFields combined with bevacizumab and carboplatin. CONCLUSIONS. This is the first study to demonstrate an objective metabolic response of recurrent glioblastoma within 1.5-3 months after initiation of TTFields. The data suggest that amino acid PET can identify early responders to TTFields therapy. Citation Format: Sandeep Mittal, Geoffrey R. Barger, Edit Bosnyák, Varun B. Shah, Csaba Juhász. Early metabolic response to tumor-treating fields in patients with recurrent glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3730. doi:10.1158/1538-7445.AM2017-3730

Influence of Bevacizumab on Blood-Brain Barrier Permeability and O-(2-18F-Fluoroethyl)-l-Tyrosine Uptake in Rat Gliomas.

Restoration of the blood-brain barrier (BBB) after antiangiogenic therapy of gliomas with bevacizumab may result in a decrease in contrast enhancement on MRI despite tumor progression. This so-called pseudoresponse is difficult to differentiate from a true tumor response with conventional MRI. Initial patient studies have indicated that PET using O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) may be helpful for solving this diagnostic problem. This study was performed to investigate the effects of bevacizumab on BBB permeability and 18F-FET uptake in a human xenograft model. Methods: Human U87 glioblastoma cells were implanted into the striatum of immunodeficient RNU rats. 18F-FET PET scans and ex vivo autoradiography were performed in animals receiving a single high dose of bevacizumab (45 mg/kg 2 d before PET; n = 9) or in animals receiving 2 lower doses (10 mg/kg 9 and 2 d before PET; n = 10) to evaluate short-term and long-term effects on the BBB, respectively, and in control animals without bevacizumab treatment (n = 8). Time-activity curves, slope, and tumor-to-brain ratios of 18F-FET uptake (18-61 min after injection) were evaluated using a volume-of-interest analysis. After PET scanning, Evans blue dye (EBD) was injected into animals, and cryosections of the brains were evaluated by autoradiography, by histology, and for EBD fluorescence to assess BBB permeability. Results: Compared with the control, short-term bevacizumab therapy resulted in a trend toward BBB restoration (P = 0.055) and long-term therapy resulted in a significant decrease (P = 0.004) in BBB permeability, as assessed by EBD fluorescence. In contrast, no significant differences in tumor-to-brain ratios or slope of 18F-FET uptake were observed in PET and autoradiography (P > 0.05). Conclusion:8F-FET uptake in glioblastomas seems to be largely independent of BBB permeability and reflects the viability of tumor tissue during antiangiogenic therapy more reliably than contrast-enhanced MRI.

MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation

ObjectivesTo assess specific imaging characteristics after irreversible electroporation (IRE) for locally advanced pancreatic carcinoma (LAPC) with contrast-enhanced (ce)MRI and ceCT, and to explore the correlation of these characteristics with the development of recurrence.MethodsQualitative and quantitative analyses of imaging data were performed on 25 patients treated with percutaneous IRE for LAPC. Imaging characteristics of the ablation zone on ceCT and ceMRI were assessed over a 6-month follow-up period. Contrast ratio scores between pre- and post-treatment were compared. To detect early imaging markers for treatment failure, attenuation characteristics at 6 weeks were linked to the area of recurrence within 6 months.ResultsPost-IRE, diffusion-weighted imaging (DWI)-b800 signal intensities decreased in all cases (p < 0.05). Both ceMRI and ceCT revealed absent or decreased contrast enhancement, with a hyperintense rim on ceMRI. Ablation zone volume increase was noted on both modalities in the first 6 weeks, followed by a decrease (p < 0.05). In the patients developing tumour recurrence (5/25), a focal DWI-b800 hyperintense spot at 6 weeks predated unequivocal recurrence on CT.ConclusionThe most remarkable signal alterations after pancreatic IRE were shown by DWI-b800 and ceMRI. These early imaging characteristics may be useful to establish technical success and predict treatment outcome.Key Points• This study describes imaging characteristics after irreversible electroporation (IRE) for pancreatic adenocarcinoma.• Familiarity with typical post-IRE imaging characteristics helps to interpret ablation zones.• Post-IRE, no central and variable rim enhancement are visible on contrast-enhanced imaging.• DWI-b800 may prove useful to predict early tumour recurrence.• Post-IRE examinations reveal an initial volume increase followed by a decrease.

Abstract 525: Cases with Uncommon Anti-phospholipid Antibody Syndrome Developed Multifocal Vascular Disorders Such as Ischemic Enteritis, Portal Vein Thrombosis, Ischemic Heart Disease and Cerebral Infarction

Purpose: We report cases with uncommon anti-phosholipid antibody syndrome developed ischemic enteritis, portal vein thrombosis, ischemic heart disease and cerebral infarction. The difficulty in diagnosing and treatment procedures for multifocal vascular disorders is discussed. Patients and Methods: Patient 1, 76-year-old man, with acute abdomen. Patient 2, 54-year-old man, with intractable esophageal varices. Clinical manifestation was superior mesenteric artery (SMA) thrombosis in the patient 1 and portal vein thrombosis in the patient 2. Serial CT scans were examined on 64 or 80 multidetector-row CT (Toshiba), with bolus injection of contrast media for CT angiography (CTA). Abdominal angiography with endovascular intervention and coronary angiography were performed on Allura Xper FD-20 and FD-10 (Philips). Results: Emergency CTA of patient 1 showed decreased contrast enhancement of SMA and SMV but enhancement of intestinal walls were well preserved. Although the patient’s symptom got better, follow-up CT revealed the growth of SMA thrombosis. The aspiration and the dissolution of SMA thrombosis were performed through the SMA catheter for five days resulted in complete recanalization.Then he felt chest oppression and 75% stenosis of RCA segment 4, followed by complete spastic occlusion on Acetylcholine loading on the coronary angiography, which recovered perfectly with intra-coronary nitroglycerin administration. He discharged our hospital with health, while he had cerebellar infarction with right cerebellar artery occlusion. On patient 2, to resolve portal hypertension, balloon-occluded retrograde transvenous obliteration was scheduled, however, due to numerous collaterals prevented the effective venous obliteration and splenic arterial embolization was selected alternatively. Discussion and Conclusions: The progressive SMA thrombosis with coronary disease and subsequent cerebellar occlusion seen in patient 1, and the portal vein thrombosis in patient 2 without chronic hepatitis nor cirrhosis were unusual. To discover underlining uncommon anti-phosholipid antibody syndrome is important to prevent serious vascular diseases in sequence.

Ultrasound features of hepatocellular adenoma and the additional value of contrast-enhanced ultrasound

Hepatocellular adenoma (HCA) is a rare benign tumor of the liver. It is of clinical importance to differentiate HCA from other liver tumors, especially hepatocellular carcinoma (HCC). This study aimed to evaluate the characteristic features of HCA by conventional ultrasound and contrast-enhanced ultrasound (CEUS) findings. Twenty-six patients (10 males and 16 females; mean age 36.2+/-5.0 years) with 26 histopathologically proven HCAs were retrospectively identified. According to the maximum diameter of HCAs, they were divided into three groups: <30 mm, 30-50 mm, and >50 mm. Ultrasound examinations were performed with C5-2 broadband curved transducer of Philips iU22 unit (Philips Bothell, WA, USA). For each lesion, a dose of 2.4 mL SonoVue® (Bracco Imaging Spa, Milan, Italy) was injected as a quick bolus into the cubital vein. Lesions' echogenicity, color-Doppler flow imaging and contrast enhancement patterns were recorded. Grayscale ultrasound revealed that most of HCAs were hypoechoic (73.1%, 19/26). Spotty calcifications were detected in 26.9% (7/26) of the lesions. Color-Doppler flow imaging detected centripetal bulky color flow in 46.2% (12/26) of the HCAs. CEUS showed that 73.1% (19/26) of the HCAs displayed as rapid, complete and homogenous enhancement, and 53.8% (14/26) showed decreased contrast enhancement in the late phase. There was no significant difference in enhancement patterns among different sizes of HCAs (P>0.05). Centripetal enhancement with subcapsular tortuous arteries was common in larger HCAs. CEUS combined with grayscale and color-Doppler flow imaging helped to improve preoperative diagnosis of HCAs. The characteristic imaging features of HCAs included: rapid homogeneous enhancement and slow wash-out pattern on CEUS; heterogeneous echogenicity on grayscale ultrasound; and centripetal enhancement with subcapsular tortuous arteries in large HCAs.

Risk Factors for Femoral Head Deformity in the Early Stage of Legg-Calvé-Perthes Disease: MR Contrast Enhancement and Diffusion Indexes.

To determine whether changes in diffusion and/or contrast enhancement are of prognostic value in the early stage of Legg-Calvé-Perthes disease (LCPD). This study was approved by the institutional review board, and written informed consent was obtained from patient parents. Diffusion and contrast agent-enhanced magnetic resonance (MR) imaging studies were performed in 46 children (37 boys and nine girls; mean age, 7.5 years [age range, 3.3-11.9 years]) with unilateral LCPD at the early stage before development of extensive femoral head deformity. The degree of contrast enhancement was measured on the contrast-enhanced MR images, and the apparent diffusion coefficient (ADC) value was measured on the ADC map at various regions of interest in the proximal femur. The association of the MR imaging parameters that compared the affected side with the contralateral normal side with the femoral head deformity index value above 0.3 at 2 years was investigated. Increased diffusion in the metaphysis (P = .003) and decreased contrast enhancement in the central epiphysis (P = .034) were the significant prognostic indicators of subsequent femoral head deformation. ADC in the metaphysis 45% higher and a contrast enhancement in the central epiphysis 37% lower than those of the contralateral normal side are associated with a nonfavorable prognosis. For diffusion MR imaging, sensitivity was 83% (15 of 18), specificity was 86% (24 of 28), positive predictive value was 79% (15 of 19), negative predictive value was 89% (24 of 27), and accuracy was 85% (39 of 46). For contrast-enhanced MR imaging, sensitivity was 78% (14 of 18), specificity was 64% (18 of 28), positive predictive value was 58% (14 of 24), negative predictive value was 82% (18 of 22), and accuracy was 70% (32 of 46). Diffusion and contrast-enhanced MR imaging are potentially useful to assess risk of later development of femoral head deformity.

P16.09 * VALUE OF FET-PET EVALUATION IN PATIENTS TREATED WITH AXITINIB

INTRODUCTION: VEGF/VEGFR targeted therapy for recurrent glioblastoma (rGB) normalizes tumour vasculature and restores the blood-brain barrier (BBB), resulting in decreased contrast enhancement and reduced peritumoral oedema. MRI-T2/FLAIR images are useful to document non-contrast-enhancing tumor progression, but its specificity is limited. Since the uptake of Fluoroethyltyrosine in GB reflects tumor metabolism and not BBB-integrity, the extent of (18)F-fluoroethyltyrosine (FET) uptake, as assessed by positron emission tomography (PET), may be of value in assessing the tumor response to treatment with small molecule VEGFR-inhibitors such as axitinib., MATERIAL AND METHODS: We evaluated patients with rGB treated with axitinib with MRI and FET-PET (static images acquired 45 min. after tracer administration) at baseline. In patients demonstrating a response on MRI (using RANO criteria), FET-PET was repeated. For 18F-FET PET, reduction of the metabolically active volume (Sum of tumour associated pixels with target-to-normal brain ratio of ≥1.5) was considered as a metabolic response to treatment. RESULTS: 15 patients treated with axitinib were evaluated with MRI and FET-PET. On MRI, 2 pts had CR and 4 PR. All responses on MRI were also characterized by a decrease in FET-active tumor volume. The extent of reduction of metabolically active volume did not correlated with the extent of tumor regression on Gd- MRI: the 2 patients with CR on MRI had a 65% and 43% decrease on FET-PET, respectively, whereas the decrease on FET-PET ranged between 26 and 100% in the patients with PR on MRI. A trend was observed between a higher baseline FET-active tumor volume and an increased progression-free survival (PFS) and overall survival (OS). A greater reduction of the metabolically active volume did correlate with longer PFS and OS (logrank p > 0,001 and p < 0,025, respectively). CONCLUSION: In patients with rGB treated with the VEGFR-inhibitor axitinib, baseline FET-PET has prognostic value. Response evaluation based on FET-PET is complementary to MRI based assessment and may prove superior in predicting survival on treatment with axitinib. Our preliminary findings deserve further evaluation in a larger series.

Quantitative and Qualitative Assessment of Bone Perfusion and Arterial Contributions in a Patellar Fracture Model Using Gadolinium-Enhanced Magnetic Resonance Imaging

The purpose of the present study was to evaluate the anatomy and contribution of the patellar vascular supply and to quantify the effect of a transverse fracture on patellar perfusion. In twenty matched pairs of fresh-frozen cadaveric knees, the superficial femoral artery, anterior tibialis artery, and posterior tibialis artery were cannulated. One side of each matched pair was randomly selected to undergo one of two osteotomies: (1) midpatellar osteotomy or (2) distal-pole osteotomy. For volumetric analysis, comparisons were performed between contrast-enhanced magnetic resonance images and precontrast magnetic resonance images as well as between osteotomized patellar bone fragments and the corresponding intact areas on the control side. We then injected a urethane polymer compound and dissected all specimens to examine extraosseous vascularity. Magnetic resonance imaging demonstrated that the largest arterial contribution to the patella entered at the inferior pole in 100% of the specimens; in 80% of these specimens, the artery entered inferomedially. It also revealed an overall decrease in contrast enhancement in both transverse osteotomy groups, with an average reduction in enhancement in the proximal fragment of 36%. If possible, surgical interventions about the knee should be carefully planned to preserve the peripatellar ring (the source of the entire patellar blood supply), especially the inferior patellar network. Distal-pole patellectomy should be avoided to retain vascularized bone at the reduced fracture site.

Human chorionic gonadotropin elevation is not an intracranial germ cell tumor signature

Dear editor, For many years, in case of suspicion of a germ cell tumor (GCT), human chorionic gonadotropin (HCG), its beta subunit and alpha-fetoprotein (AFP) have been used as specific markers in the blood and/or cerebrospinal fluid (CSF) for clinical decision-making [4]. A positive test is an indication for treatment, without requiring histological confirmation [5]. We report a first description of CSF HCG elevation in a non-cystic suprasellar craniopharyngioma, contradicting this dogma. A 52-year-old male with a history of arterial hypertension and tinnitus complained of a decrease in left-side visual acuity over a few weeks, associated with polyuro-polydipsia syndrome. MRI examination revealed a suprasellar lesion of 16×18×16 mm, with a moderate hyper-T2 signal and an iso-T1 signal with homogeneous gadolinium enhancement. The lesion did not have a cystic component (see Fig. 1). Spinal MRI was negative, and the cerebral CT scan did not show any calcification of the tumor. Hormone analysis revealed a pituitary deficiency. Biological analysis of the CSF performed as part of the etiological assessment revealed an elevation of HCG to 10.8 IU/l (normal levels <5 IU/l) and of free beta-HCG to 1.1 ng/ml (normal levels <0.1 IU/l). Elevation of AFP was not detected in the blood or CSF. No abnormal cells were found in the CSF. No elevation of these markers was found in the blood. Given the many atypical features in our patient, we decided to perform a robot-assisted stereotaxic biopsy. The final diagnosis was papillary craniopharyngioma and excluded germinoma. Due to the high risk of surgical treatment, and after a multidisciplinary discussion, the tumor was treated by radiotherapy. Six months after that, the patient recovered his visual field loss, but the hypopituitarism remained. The MRI showed a volumetric reduction of the tumor and a decrease in contrast enhancement. This report points out two issues: First, some authors [2, 3, 6] have suggested that many cystic pineal, sellar or suprasellar lesions, including cystic craniopharyngioma, are able to produce theses markers through their wall (descriptions of HCG in benign pineal cyst contents and walls). This observation of a solid craniopharyngioma demonstrates for the first time that the tumor itself is able to secrete low levels of HCG and β-HCG that may be detectable in the CSF. CSF AFP elevation was also detected in two cases of craniopharyngiomas, one of which was proven to be a malignant form [2]. So far, no blood elevation of these markers has been reported in craniopharyngiomas. Second, therefore, physicians involved in brain management need to be aware that HCG or AFP CSF positivity in a patient with a suprasellar tumor is not a specific GCT signature and is not enough information for making therapeutic decisions. Our clinical case underlines the importance of multidisciplinary discussions and the necessity to perform a biopsy in patients showing isolated suprasellar lesions (bipolar pineal and suprasellar locations remain suggestive of germinoma), positive for CSF markers but with atypical P. Bourdillon (*) : E. Jouanneau Department of neurosurgery A, Hopital Neurologique et Neurochirurgical Pierre Wertheimer, Hospices Civils de Lyon, 59 bd Pinel, 69500 Bron, France e-mail: pierre.bourdillon@neurochirurgie.fr