Areas Of Contrast Enhancement Research Articles

T2 Fluid-Attenuated Inversion Recovery Resection for Glioblastoma Involving Eloquent Brain Areas Facilitated Through Awake Craniotomy and Clinical Outcome

Despite evidence that a greater extent of resection (EOR) improves survival, the role of extended resection based on magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) in the prognosis of glioblastoma (GBM) remains controversial. This study aims to investigate the role of additional resection of FLAIR-detected abnormalities and its influence on clinical outcomes of patients with GBM. Forty-six patients with newly diagnosed GBM involving eloquent brain areas were included. Surgeries were performed using awake craniotomy (AC) or AC combined with sodium fluorescein (SF) guidance. Following total removal of the contrast-enhancing tumor area, the EOR of FLAIR abnormalities was dichotomized to identify the best separation threshold for progression-free survival (PFS), overall survival (OS), and 30-day postoperative neurologic function of patients with GBM. The threshold for removal of FLAIR abnormalities affecting survival was determined to be 25%. The median OS and PFS were shorter in the group with FLAIR resection <25% compared with the group with FLAIR resection ≥25% (12 months vs. 26 months; P= 0.001 and 6months vs. 15 months; P= 0.016, respectively). Univariate and multivariate analyses identified tumor location within or near the eloquent brain areas and the 25%threshold for FLAIR EOR as independent factors affecting OS and PFS. Identifying a feasible threshold for the resection of FLAIR abnormalities is valuable in improving the survival of patients with GBM. Extended resection of GBM involving eloquent brain areas was safe when using a combination of AC and SF-guided surgery.

Delivering the diluted contrast agent with saline via a spiral flow tube improves arterial enhancement for contrast enhancement of magnetic resonance angiography of the neck: A retrospective study.

A contrast agent can be pushed by a saline solution more effectively through a spiral flow tube than through a conventional T-shaped tube in contrast-enhanced magnetic resonance angiography (CEMRA). To compare the degree of contrast enhancement and signal stability in the carotid artery by using CEMRA between a spiral flow tube and a T-shaped tube.A total of 100 patients were analyzed in this retrospective study. The first 50 patients underwent CEMRA of the carotid artery with the T-shaped tube, while the last 50 patients used the spiral flow tube. Gadoterate meglumine was diluted with saline to make a total volume of 20 mL. Injection was performed with a bolus rate of 2.5 mL/s for 8 seconds. Five regions of interest (ROIs) were placed on the contrast-enhanced area in each carotid artery and the signal intensity (SI) in the ROI was used for the analysis. The ROIs on the brain stem were also placed and the average SI in this ROI was used as a reference signal. The enhancement of the artery (E artery) was calculated as a normalized signal using the following equation: E artery = SI in the ROI of the carotid bifurcation/SI in the ROI of the brain stem. Signal homogeneity in the contrast-enhanced area (SHenhance) was assessed by calculating the coefficient of variation from the SI in the 5 ROIs. The value of SHenhance and E artery between the data obtained from the spiral flow tube and the T-shaped tube were compared. P-values <.05 were considered significant.We found a significant difference in SHenhance between the data obtained from the spiral flow tube (0.20 ± 0.060) and the T-shaped tube (0.24 ± 0.056) (P = .001). The E artery values significantly increased by 15% (spiral flow tube, median 14.1 with interquartile range [IQR] 11.8–15.4 vs T-shaped tube, median 12.3 IQR 11.3–14.0, P = .02) using the spiral flow tube.These findings suggest that, by using the Spiral flow tube, the homogeneity of the contrast-enhanced signal intensity in the carotid artery was significantly improved without decreasing the signal intensity in CEMRA.

Complex Dysembryoplastic Neuroepithelial Tumor With Pilocytic Astrocytoma Component

Abstract Objectives Dysembryoplastic neuroepithelial tumor (DNET) is an uncommon mixed glioneuronal tumor. DNET is classified as WHO grade I neoplasm and commonly seen in the temporal lobe of children and young adults with features of pharmacoresistant seizures. The term complex DNET defines those tumors associated with additional features, including a pilocytic astrocytoma (PA) component, a finding that is rarely described in the literature. Methods Here we report a 16-year-old male who presented with seizures. On imaging, a 5.5 × 2.2 × 2.1-cm multiloculated mass was centered in the left frontoparietal gray matter with solid and cystic components and focal areas of contrast enhancement. Results Microscopic examination revealed a noninfiltrative glioneuronal neoplasm composed of a bland population of round to oval cells arranged around pools of mucinous material. Occasional large neuronal cells were noted. Focal areas composed of elongated astrocytic cells demonstrating piloid morphology were also present. No high-grade features were demonstrated. The findings are consistent with DNET, complex form in addition to a second component with piloid features resembling pilocytic astrocytoma. Conclusion The early recognition of DNET is important as it has an excellent prognosis on complete surgical excision without use of adjunct therapies. Unresected or incompletely removed DNET and secondary radiochemotherapy may give rise to recurrence and malignancy. The development of the secondary neoplasm challenges the stability in terms of biological behavior and highlights the importance of complete surgical excision and close follow-up. Our patient had neither undergone previous surgery nor received any adjuvant therapy, and hence this case is a de novo development of PA in a DNET. The association of contrast enhancement with DNET is an unusual finding in this case.

P06.02 Tumor Treating Fields therapy application in 3-year-old grade 4 glioma patient is feasible and safe

Abstract BACKGROUND High-grade gliomas (HGG) are aggressive brain tumors affecting both children and adults. In adult patients a new treatment modality was recently established for patients with newly diagnosed (nd) and recurrent glioblastoma (GBM). Low intensity intermediate frequency alternating electric fields, known as Tumor Treating Fields (TTFields), demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in adult ndGBM patients. For pediatric HGG patients only few treatment options are available. Here, we report on a pediatric patient who is receiving TTFields therapy in combination with temozolomide. MATERIAL AND METHODS A three-year-old male presented with a grade IV glioma with H3K27M expression located pontine on the right occipital. A stereotactic biopsy was performed; further analysis revealed no IDH1 mutation, no TERT promoter mutation and no MGMT promoter methylation. The patient recieved radiochemotherapy with temozolomide. TTFields therapy was initiated after completion of radiochemotherapy in combination with temozolomide. Due to the location of the tumor, the infratentorial transducer array layout was used for TTFields application. RESULTS At the beginning of TTFields therapy the patient and his family needed time to get used to the new therapy, due to this the adherence to TTFields therapy was on a low level in the first month. The TTFields usage rate improved every month from about 40 % in the first two months to about 80 % after 5 and 6 months. After the initial time for adaption to the therapy, the average usage rate in months 4 to 8 was 75.87 %, which is above the independent prognostic threshold of 75 %. The patient is on TTFields therapy for more than 8 months and no therapy-related adverse events were observed during this time. To-date the patient is still on TTFields therapy and clinically stable. MRI analysis revealed stable disease with a slightly reduced area of contrast-enhancement. CONCLUSION In this case, the TTFields usage rate was low in the beginning, the patient and his relatives demonstrated a successful adaption to the therapy over time. This case demonstrates that TTFields therapy can be continued at high adherence, although the usage rate might be low in the beginning. Moreover, in this presented patient TTFields therapy is feasible and safe in a pediatric patient at 3 years of age at initiation of therapy. In conclusion, TTFields therapy can be offered to pediatric patients with HGG. Safety and efficacy in pediatric patients should be further investigated in clinical trials.

IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein-specific PET/CT.

Targeting fibroblast activation protein (FAP) is a new diagnostic approach allowing the visualization of tumor stroma. Here, we applied FAP-specific PET imaging to gliomas. We analyzed the target affinity and specificity of two FAP ligands (FAPI-02 and FAPI-04) in vitro, and the pharmacokinetics and biodistribution in mice in vivo. Clinically, we used 68Ga-labeled FAPI-02/04 for PET imaging in 18 glioma patients (five IDH-mutant gliomas, 13 IDH-wildtype glioblastomas). For binding studies with 177Lu-radiolabeled FAPI-02/04, we used the glioblastoma cell line U87MG, FAP-transfected fibrosarcoma cells, and CD26-transfected human embryonic kidney cells. For pharmacokinetic and biodistribution studies, U87MG-xenografted mice were injected with 68Ga-labeled compounds followed by small-animal PET imaging and 177Lu-labeled FAPI-02/04, respectively. Clinical PET/CT scans were performed 30min post intravenous administration of 68Ga-FAPI-02/04. PET and MRI scans were co-registrated. Immunohistochemistry was done on 14 gliomas using a FAP-specific antibody. FAPI-02 and FAPI-04 showed high binding specificity to FAP. FAPI-04 demonstrated higher tumor accumulation and delayed elimination compared with FAPI-02 in preclinical studies. IDH-wildtype glioblastomas and grade III/IV, but not grade II, IDH-mutant gliomas showed elevated tracer uptake. In glioblastomas, we observed spots with increased uptake in projection on contrast-enhancing areas. Immunohistochemistry showed FAP-positive cells with mainly elongated cell bodies and perivascular FAP-positive cells in glioblastomas and an anaplastic IDH-mutant astrocytoma. Using FAP-specific PET imaging, increased tracer uptake in IDH-wildtype glioblastomas and high-grade IDH-mutant astrocytomas, but not in diffuse astrocytomas, may allow non-invasive distinction between low-grade IDH-mutant and high-grade gliomas. Therefore, FAP-specific imaging in gliomas may be useful for follow-up studies although further clinical evaluation is required.

Correlation between magnetic resonance imaging characteristics and BRAF alteration status in individuals with optic pathway/hypothalamic pilocytic astrocytomas

Background and purposeMost individuals with optic pathway/hypothalamic pilocytic astrocytoma (OPHPA) harbor either the BRAF V600E mutation or KIAA1549-BRAF fusion (K-B). This study aimed to investigate the imaging characteristics of OPHPA in relation to BRAF alteration status. Materials and methodsSeven cases of OPHPA harboring either the BRAF V600E mutation or K-B fusion were included in the study. Preoperative magnetic resonance imaging (MRI) was assessed for degree of T2 hyperintensity on T2-weighted images (T2WI) and the ratio of nonenhancing T2 or fluid-attenuated inversion recovery (FLAIR) hyperintense area to the contrast enhanced area (CE) on gadolinium-enhanced-T1 weighted images (T2/FLAIR-CE mismatch). The T2 signal intensity was normalized to cerebrospinal fluid (T2/CSF) for both the V600E and K-B group and compared. T2/FLAIR-CE mismatch was assessed by calculating the proportion of the tumor volume of nonenhancing high T2 signal intensity to the whole lesion (nonenhancing and enhancing components). ResultsFour and three cases of OPHPA harboring the BRAF V600E mutation and K-B, respectively, were analyzed. The T2/CSF value was higher in the K-B group than in the V600E group. Moreover, the V600E group had a larger T2/FLAIR-CE mismatch than the K-B group. ConclusionsThe BRAF alteration status in individuals with OPHPA was associated with preoperative MRI by focusing on T2 signal intensity and T2/FLAIR-CE mismatch. The BRAF V600E mutation was associated with a lower T2/CSF value and larger T2/FLAIR-CE mismatch, whereas K-B fusion was associated with a higher T2/CSF value and smaller T2/FLAIR-CE mismatch.

Association between Tumor Acidity and Hypervascularity in Human Gliomas Using pH-Weighted Amine Chemical Exchange Saturation Transfer Echo-Planar Imaging and Dynamic Susceptibility Contrast Perfusion MRI at 3T.

Acidification of the tumor microenvironment from abnormal metabolism along with angiogenesis to meet metabolic demands are both hallmarks of malignant brain tumors; however, the interdependency of tumor acidity and vascularity has not been explored. Therefore, our aim was to investigate the association between pH-sensitive amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) and relative cerebral blood volume (CBV) measurements obtained from dynamic susceptibility contrast (DSC) perfusion MRI in patients with gliomas. In this retrospective study, 90 patients with histologically confirmed gliomas were scanned between 2015 and 2018 (median age, 50.3 years; male/female ratio = 59:31). pH-weighting was obtained using chemical exchange saturation transfer echo-planar imaging estimation of the magnetization transfer ratio asymmetry at 3 ppm, and CBV was estimated using DSC-MR imaging. The voxelwise correlation and patient-wise median value correlation between the magnetization transfer ratio asymmetry at 3 ppm and CBV within T2-hyperintense lesions and contrast-enhancing lesions were evaluated using the Pearson correlation analysis. General colocalization of elevated perfusion and high acidity was observed in tumors, with local intratumor heterogeneity. For patient-wise analysis, median CBV and magnetization transfer ratio asymmetry at 3 ppm within T2-hyperintense lesions were significantly correlated (R = 0.3180, P = .002), but not in areas of contrast enhancement (P = .52). The positive correlation in T2-hyperintense lesions remained within high-grade gliomas (R = 0.4128, P = .001) and in isocitrate dehydrogenase wild-type gliomas (R = 0.4300, P = .002), but not in World Health Organization II or in isocitrate dehydrogenase mutant tumors. Both magnetization transfer ratio asymmetry at 3 ppm and the voxelwise correlation between magnetization transfer ratio asymmetry and CBV were higher in high-grade gliomas compared with low-grade gliomas in T2-hyperintense tumors (magnetization transfer ratio asymmetry, P = .02; Pearson correlation, P = .01). The same trend held when comparing isocitrate dehydrogenase wild-type gliomas and isocitrate dehydrogenase mutant gliomas (magnetization transfer ratio asymmetry, P = .04; Pearson correlation, P = .01). A positive linear correlation between CBV and acidity in areas of T2-hyperintense, nonenhancing tumor, but not enhancing tumor, was observed across patients. Local heterogeneity was observed within individual tumors.

Utility of sodium fluorescein for achieving resection targets in glioblastoma: increased gross- or near-total resections and prolonged survival.

It is commonly reported that achieving gross-total resection of contrast-enhancing areas in patients with glioblastoma (GBM) improves overall survival. Efforts to achieve an improved resection have included the use of both imaging and pharmacological adjuvants. The authors sought to investigate the role of sodium fluorescein in improving the rates of gross-total resection of GBM and to assess whether patients undergoing resection with fluorescein have improved survival compared to patients undergoing resection without fluorescein. A retrospective chart review was performed on 57 consecutive patients undergoing 64 surgeries with sodium fluorescein to treat newly diagnosed or recurrent GBMs from May 2014 to June 2017 at a teaching institution. Outcomes were compared to those in patients with GBMs who underwent resection without fluorescein. Complete or near-total (≥ 98%) resection was achieved in 73% (47/64) of fluorescein cases. Of 42 cases thought not to be amenable to complete resection, 10 procedures (24%) resulted in gross-total resection and 15 (36%) resulted in near-total resection following the use of sodium fluorescein. No patients developed any local or systemic side effects after fluorescein injection. Patients undergoing resection with sodium fluorescein, compared to the non-fluorescein-treated group, had increased rates of gross- or near-total resection (73% vs 53%, respectively; p < 0.05) as well as improved median survival (78 weeks vs 60 weeks, respectively; p < 0.360). This study is the largest case series to date demonstrating the beneficial effect of utilizing sodium fluorescein as an adjunct in GBM resection. Sodium fluorescein facilitated resection in cases in which it was employed, including dominant-side resections particularly near speech and motor regions. The cohort of patients in which sodium fluorescein was utilized had statistically significantly increased rates of gross- or near-total resection. Additionally, the fluorescein group demonstrated prolonged median survival, although this was not statistically significant. This work demonstrates the promise of an affordable and easy-to-implement strategy for improving rates of total resection of contrast-enhancing areas in patients with GBM.

Bronchial angiolipoma successfully treated by sleeve resection of the right bronchus intermedius: a case report

BackgroundAngiolipoma is a rare, benign tumor that primarily develops in the limbs and trunk. The occurrence of angiolipoma in the lungs is extremely rare; to date, only two cases of primary bronchial angiolipoma have been reported. Here, we report a case of angiolipoma of the right bronchus intermedius that was successfully treated with sleeve resection and reconstructive surgery.Case presentationThis report presents a case of angiolipoma that developed in the right bronchus intermedius of a 68-year-old man. A chest CT revealed a 10-mm endobronchial mass that was clearly visible as a high-attenuation area of contrast enhancement. Bronchoscopy revealed a submucosal tumor on the anterior wall of the entrance to the right bronchus intermedius that was constricting the airway lumen. The tumor surface was covered with numerous engorged blood vessels, and the middle and inferior pulmonary lobes were intact. Bronchial sleeve resection of the right bronchus intermedius was performed. Histologically, a mixture of proliferating blood vessels and adipocytes were observed within the bronchus wall. Therefore, the pathological diagnosis was angiolipoma. Lung function was preserved, and complete resection of the tumor was achieved. At present (2 years and 7 months after surgery), the patient is recurrence-free.ConclusionAccordingly, using bronchial sleeve resection and end-to-end anastomosis techniques, we accomplished complete tumor excision and avoided the need to resect additional lung parenchyma. Our procedure preserved pulmonary function and yielded a curative result. Bronchoscopic intervention or minimal parenchymal resection should be considered as treatments for bronchial angiolipoma. Given the small number of reports of bronchial angiolipoma, the collection of additional data is important to elucidate the clinical characteristics of this rare tumor.

Predictive markers for MGMT promoter methylation in glioblastomas.

The promoter methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene has been described as the most important predictor of chemotherapeutic response and patients' survival in glioblastomas (GBs). Therefore, prediction of the MGMT promoter methylation status by imaging would help to preoperatively decide the overall treatment strategy as well as surgical strategy. This study aimed to detect imaging parameters to predict MGMT promoter methylation in GBs by using a commercially available software. We investigated three imaging features (ring enhancement, tumor location, and laterality) and apparent diffusion coefficient (ADC) parameters in 48 newly diagnosed GBs treated at Keio University Hospital in 2006 or later. For ADC, texture analyses were performed. Regions of interest (ROIs) were drawn manually with reference to contrast-enhanced areas, excluding necrotic and cystic regions. Mean ADC value and ADC histogram parameters, including kurtosis, skewness, and entropy, were compared with MGMT promoter methylation. Each parameter was evaluated to determine correlation with MGMT promoter methylation, and the parameters with significant associations with the methylation status were correlated with the MGMT-positive cell ratio determined by immunohistochemistry (IHC) analysis. The mean ADC value and ADC entropy were significantly associated with MGMT promoter methylation. The combination of mean ADC value and ADC entropy predicted MGMT promoter methylation, with a PPV of 81.2% and specificity of 88.9%. The mean ADC value and ADC entropy were negatively correlated with the MGMT-positive cell ratio in the IHC analysis. This study demonstrated that texture analyses of ADC histograms in GBs were predictive of MGMT promoter methylation.

Multimodal MRI characteristics of the glioblastoma infiltration beyond contrast enhancement.

Our inability to identify the invasive margin of glioblastomas hampers attempts to achieve local control. Diffusion tensor imaging (DTI) has been implemented clinically to delineate the margin of the tumor infiltration, its derived anisotropic (q) values can extend beyond the contrast-enhanced area and correlates closely with the tumor. However, its correlation with tumor infiltration shown on multivoxel proton magnetic resonance spectroscopy1 (MRS) and perfusion magnetic resonance imaging (MRI) should be investigated. In this study, we aimed to show tissue characteristics of the q-defined peritumoral invasion on MRS and perfusion MRI. Patients with a primary glioblastoma were included (n = 51). Four regions of interest were analyzed; the contrast-enhanced lesion, peritumoral abnormal q region, peritumoral normal q region, and contralateral normal-appearing white matter. MRS, including choline (Cho)/creatinine (Cr), Cho/N-acetyl-aspartate (NAA) and NAA/Cr ratios, and the relative cerebral blood volume (rCBV) were analyzed. Our results showed an increase in the Cho/NAA (p = 0.0346) and Cho/Cr (p = 0.0219) ratios in the peritumoral abnormal q region, suggestive of tumor invasion. The rCBV was marginally elevated (p = 0.0798). Furthermore, the size of the abnormal q regions was correlated with survival; patients with larger abnormal q regions showed better progression-free survival (median 287 versus 53 days, p = 0.001) and overall survival (median 464 versus 274 days, p = 0.006) than those with smaller peritumoral abnormal q regions of interest. These results support how the DTI q abnormal area identifies tumor activity beyond the contrast-enhanced area, especially correlating with MRS.

Provisional results of contrast-enhanced ultrasonography of breast tumors (JABTS FLOW-CEUS01 study -part 1-)

Background Contrast-enhanced ultrasonography (CEUS) of the breast with perflubutane (Sonazoid®) was conducted for detecting mammary tumors and expanded in August 2012. This study shows typical images of benign and malignant tumors; however, these images are now out-of-date owing to performance improvements in ultrasonic devices. Therefore, Flow Imaging Research Group, the Japan Association of Breast and Thyroid Sonology (JABTS), examined the contrast pattern of benign and malignant tumors using CEUS (JABTS FLOW-CEUS01, UMINID: 000026289). Purpose The JABTS FLOW-CEUS01 multicenter study aims to select typical CEUS images of benign and malignant tumors and reevaluate diagnostic criteria based on this data. We first present diagnostic criteria based on extracted educational cases. Materials and Methods Two hundred and eighteen breast tumors from nine institutions that have performed CEUS with perflubutane (Sonazoid®) followed by histological examinations were used in this study. After evaluating 30 educational cases extracted from among all registered cases, we proposed CEUS findings and criteria for differential diagnosis between benign and malignant breast tumors. The remaining 188 cases were used for diagnosing sets diagnosed by three blind readers. Based on the new findings and criteria, the diagnostic accuracy of CEUS of breast tumors was evaluated. This study was approved by the Ethics Committee and institutional review board of Toho University Omori Medical Center. Results As CEUS findings for differential diagnosis, five contrast-enhancement patterns (shapes, margins, defects of stains, intensity, and homogeneity), three vascular patterns (tree-like appearance, surrounding marginal vessels, plunging or penetrating vessels), and a range of contrast-enhanced areas were selected. These nine findings were adopted as criteria in this study.

Multicenter study to evaluate the difference between benign and malignant breast tumors by contrast-enhanced ultrasonography (JABTS FLOW-CEUS 01 study -part 2-)

Background Contrast-enhanced ultrasonography (CEUS) of the breast using perflubutane (Sonazoid®) has been utilized for over 6 years in Japan. Owing to advances in equipment and technology, reevaluation of CEUS findings and diagnostic criteria is of importance. Therefore, in the present study, we examined the contrast patterns of benign and malignant lesions on CEUS (JABTS FLOW-CEUS01, UMINID: 000026289). Objective First, we aimed to select typical CEUS images of malignant and benign breast tumors. Second, we aimed to reevaluate the diagnostic criteria for CEUS of breast tumors. Methods Two hundred and eighteen breast tumors from nine institutions evaluated using CEUS and subsequently histological examinations were analyzed in the present study. After evaluation of 30 educational cases that were extracted from the registered cases, we proposed CEUS findings and criteria for the differential diagnosis of breast tumors. The remaining 188 cases were used for the analysis, and the diagnosis was made by three blind readers. In accordance with the new findings and criteria, the diagnostic accuracy of CEUS of breast tumors was evaluated. This study was approved by the ethics committee and institutional review board of Kobe City Nishi-Kobe Medical Center. Results The following CEUS findings were useful for the differential diagnosis: 5 contrast-enhancement patterns (shapes, margins, defects of stains, intensity, and homogeneity), 3 vascular patterns (tree-like appearance, surrounding marginal vessels, plunging or penetrating vessels), and range of contrast-enhanced areas. In the univariate analysis, all the 9 findings were significantly useful for the differential diagnosis. In the multivariate analysis, range of contrast-enhanced areas (odds ratio; 1.863, 95% confidence interval [CI] 1.356-2.560, p Conclusions The conventional CEUS findings and criteria of breast tumors were confirmed to be useful for differentiating between benign and malignant breast tumors. Additionally, range of contrast-enhanced areas was found to be helpful. Although the findings analyzed herein were characteristic CEUS features of benign and malignant breast tumors, respectively, additional diagnostic effects seem to be limited. Thus, it is important to select cases for which CEUS may be useful.

Dosimetric Impact of Automated Non-Coplanar Treatment Planning Using Stereotactic Radiosurgery for Multiple Cranial Metastases: Comparison between Hyperarc and Cyberknife Dose Distributions

The purpose of this study was to clarify the dosimetric impact of automated non-coplanar treatment planning, HyperArc-based stereotactic radiosurgery (SRS) for multiple cranial metastases by comparing with Robotic Radiosurgery System, Cyberknife planning. Eleven cancer patients with multiple cranial metastases (range of the number of tumors: 3 to 5) treated by CyberKnife M6 (Accuray Inc, Sunnyvale, USA) in the period from January 2016 to December 2017 were selected for this study. MultiPlan (Accuray Inc, Sunnyvale, USA) with Ray-tracking dose calculation algorithm was used as a radiation treatment planning system. The GTV was defined as the area of contrast enhancement on MRI and PTV was equal to GTV. The treatment dose of 23 Gy per single fraction was prescribed to the 70%-80% isodose line covering 95% of PTV. The dose to the surrounding healthy brain and organs at risk (e.g., brain stem) were optimized to minimize complications for all plans generated using our institutional protocol; PTV Dmin > 20 Gy, brainstem Dmax < 15 Gy, spinal cord Dmax < 14 Gy, optic nerve Dmax < 10 Gy, and optic chiasm Dmax < 10 Gy. These plans were replanned with an automated non-coplanar treatment planning solution implemented in a treatment planning system, named HyperArc. HyperArc plan were designed using four non-coplanar arc single-isocenter VMAT in 6MV flattening filter free mode for simulated delivery with the True beam STx (Varian) in high intensity with HD-MLC. One isocenter was used for all targets and was placed at the center of mass of all targets. Dose calculation algorithm was Acuros XB. Dosimetric differences were evaluated using target conformity/homogeneity (Paddick CI and HI), dose fall-off (gradient index) and radiation necrosis indicator (total brain V12-GTV). Summary of DVH paramters for two plans are shown in table 1. PTV CI, HI and GI were 0.60±0.11, 1.72±0.22, and 3.94±0.74, respectively, for Cyberknife plan, whereas they were 0.87±0.08, 1.44±0.05, and 5.31±1.42, respectively, for HyperArc plan (p <0.05). Total brain V12-GTV for Cyberknife and HyperArc were 5.26±2.83 cm3 and 4.02±1.71, respectively. These results showed that HyperArc plan had better CI, HI and total lung V12-GTV, although Cyberknife had better GI.Abstract TU_31_3204; Table 1DVH parameterHyperArcCyberknifePTV maximum29.78±0.9233.60±2.61 minimum20.73±0.2719.71±1.34 mean25.88±0.2727.53±1.01 HI1.44±0.051.72±0.22 CI0.87±0.080.60±0.11 GI5.31±1.423.94±0.74Total brain mean1.15±0.290.97±0.35 V12-GTV4.02±1.715.26±2.83 V2163.00±78.84151.20±89.73 Open table in a new tab We compared HyperArc and Cyberknife plans for brain multiple metastases SRS for the first time. Our results demonstrated that HyperArc-based SRS planning had the great potential for being suitable tool for brain multiple metastases SRS.

Correlation of Dynamic O-(2-[18F]Fluoroethyl)-L-Tyrosine Positron Emission Tomography, Conventional Magnetic Resonance Imaging, and Whole-Brain Histopathology in a Pretreated Glioblastoma: A Postmortem Study

Amino acid positron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine (FET) provides important additional information on the extent of viable tumor tissue of glioblastoma compared with magnetic resonance imaging (MRI). Especially after radiochemotherapy, progression of contrast enhancement in MRI is equivocal and may represent either tumor progression or treatment-related changes. Here, the first case comparing postmortem whole-brain histology of a patient with pretreated glioblastoma with dynamic invivo FET PET and MRI is presented. A 61-year-old patient with glioblastoma initially underwent partial tumor resection and died 11 weeks after completion of chemoradiation with concurrent temozolomide. Three days before the patient died, a follow-up FET PET and MRI scan indicated tumor progression. Autopsy was performed 48 hours after death. After formalin fixation, a 7-cm bihemispherical segment of the brain containing the entire tumor mass was cut into 3500 consecutive 20μm coronal sections. Representative sections were stained with hematoxylin and eosin stain, cresyl violet, and glial fibrillary acidic protein immunohistochemistry. An experienced neuropathologist identified areas of dense and diffuse neoplastic infiltration, astrogliosis, and necrosis. Invivo FET PET, MRI datasets, and postmortem histology were co-registered and compared by 3 experienced physicians. Increased uptake of FET in the area of equivocal contrast enhancement on MRI correlated very well with dense infiltration by vital tumor cells and showed tracer kinetics typical for malignant gliomas. An area of predominantly reactive astrogliosis showed only moderate uptake of FET and tracer kinetics usually observed in benign lesions. This case report impressively documents the correct imaging of a progressive glioblastoma by FET PET.

Assessing high-intensity focused ultrasound treatment of prostate cancer with hyperpolarized 13 C dual-agent imaging of metabolism and perfusion.

The goal of the study was to establish early hyperpolarized (HP) 13 C MRI metabolic and perfusion changes that predict effective high-intensity focused ultrasound (HIFU) ablation and lead to improved adjuvant treatment of partially treated regions. To accomplish this a combined HP dual-agent (13 C pyruvate and 13 C urea) 13 C MRI/multiparametric 1 H MRI approach was used to measure prostate cancer metabolism and perfusion 3-4h, 1 d, and 5 d after exposure to ablative and sub-lethal doses of HIFU within adenocarcinoma of mouse prostate tumors using a focused ultrasound applicator designed for murine studies. Pathologic and immunohistochemical analysis of the ablated tumor demonstrated fragmented, non-viable cells and vasculature consistent with coagulative necrosis, and a mixture of destroyed tissue and highly proliferative, poorly differentiated tumor cells in tumor tissues exposed to sub-lethal heat doses in the ablative margin. In ablated regions, the intensity of HP 13 C lactate or HP 13 C urea and dynamic contrast-enhanced (DCE) MRI area under the curve images were reduced to the level of background noise by 3-4h after treatment with no recovery by the 5 d time point in either case. In the tissues that received sub-lethal heat dose, there was a significant 60%±12.4% drop in HP 13 C lactate production and a significant 30±13.7% drop in urea perfusion 3-4h after treatment, followed by recovery to baseline by 5 d after treatment. DCE MRI Ktrans showed a similar trend to HP 13 C urea, demonstrating a complete loss of perfusion with no recovery in the ablated region, while having a 40%-50% decrease 3-4h after treatment followed by recovery to baseline values by 5 d in the margin region. The utility of the HP 13 C MR measures of perfusion and metabolism in optimizing focal HIFU, either alone or in combination with adjuvant therapy, deserves further testing in future studies.

Sodium Fluorescein Facilitates Guided Sampling of Diagnostic Tumor Tissue in Nonenhancing Gliomas.

Accurate tissue sampling in nonenhancing (NE) gliomas is a unique surgical challenge due to their intratumoral histological heterogeneity and absence of contrast enhancement as a guide for intraoperative stereotactic guidance. Instead, T2/fluid-attenuated inversion-recovery (FLAIR) hyperintensity on MRI is commonly used as an imaging surrogate for pathological tissue, but sampling from this region can yield nondiagnostic or underdiagnostic brain tissue. Sodium fluorescein is an intraoperative fluorescent dye that has a high predictive value for tumor identification in areas of contrast enhancement and NE in glioblastomas. However, the underlying histopathological alterations in fluorescent regions of NE gliomas remain undefined. To evaluate whether fluorescein can identify diagnostic tissue and differentiate regions with higher malignant potential during surgery for NE gliomas, thus improving sampling accuracy. Thirteen patients who presented with NE, T2/FLAIR hyperintense lesions suspicious for glioma received fluorescein (10%, 3 mg/kg intravenously) during surgical resection. Patchy fluorescence was identified within the T2/FLAIR hyperintense area in 10 of 13 (77%) patients. Samples taken from fluorescent regions were more likely to demonstrate diagnostic glioma tissue and cytologic atypia (P < .05). Fluorescein demonstrated a 95% positive predictive value for the presence of diagnostic tissue. Samples from areas of fluorescence also demonstrated greater total cell density and higher Ki-67 labeling than nonfluorescent biopsies (P < .05). Fluorescence in NE gliomas is highly predictive of diagnostic tumor tissue and regions of higher cell density and proliferative activity.

11C-methionine positron emission tomography for target delineation of recurrent glioblastoma in re-irradiation planning.

To define the optimal margin on MRI scans in the re-radiation planning of recurrent glioblastoma using methionine positron emission tomography (MET-PET). It would be very useful if the optimal margin on MRI to cover the uptake area on MET-PET is known. CT, MRI, and MET-PET were performed separately over the course of 2 weeks. Among the MRI scans, we used the contrast-enhanced T1-weighted images (Gd-MRI) and T2-weighted images (T2-MRI). The Gd-MRI-based clinical target volume (CTV) (CTV-Gd) and the T2-MRI-based CTV (CTV-T2) were defined as the contrast-enhanced area on Gd-MRI and the high intensity area on T2-MRI, respectively. We defined CTV x mm (x=5, 10, 15, 20) as x mm outside the CTV. MET-PET-based CTV (CTV-MPET) was defined as the area of accumulation of MET-PET. We calculated the sensitivity and specificity of CTV-Gd and CTV-T2 following comparison with CTV-MPET, which served as the gold standard in this study. The sensitivity of CTV-T2 5mm (98%) was significantly higher than CTV-T2 (87%), and there was no significant difference in the sensitivity between CTV-T2 5mm and CTV T2 10, 15, or 20mm. The sensitivity of CTV-Gd 20mm (97%) was lower than that of CTV-T2 5mm (98%). A margin of at least 5mm around the high intensity area on T2-MRI is necessary in the target volume delineation of recurrent glioblastoma for the coverage of MET-PET findings in re-radiation therapy planning.

Cross-sectional Areas of the Thoracic Aorta in Children and Adolescents With Repaired Tetralogy of Fallot Obtained by Cardiac Magnetic Resonance Angiography

Dilatation of the thoracic aorta is a well-known finding in corrected Tetralogy of Fallot. Complications are rare but can be life-threatening. Standard 1-dimensional (1D) measurements have several limitations. We sought to establish contrast-enhanced magnetic resonance angiography cross-sectional areas of the aorta that could serve as reference values and to identify parameters that are associated with aortic dilatation. We enrolled 101 children and adolescents. The aortic areas were measured at the level of the aortic sinus (AS), the sinotubular junction (STJ), the ascending aorta (AA), the brachiocephalic trunk (TBC), and the descending aorta (DA). Sex-specific aortic dimensions were presented as percentile curves as well as regression equations. Furthermore volumetric and functional parameters as well as clinical data were analyzed to identify parameters that are associated with aortic dilatation. Aortic areas (mm) for female subjects were 139+366×body surface area (BSA) for the AS, 134+255×BSA for the STJ, 113+239×BSA for the AA, 88+185×BSA proximal to the TBC, and 2.9+88×BSA for the DA. Aortic areas (mm) for male subjects were 162+403×BSA for the AS, 171+258×BSA for the STJ, 151+233×BSA for the AA, 73+206×BSA proximal to the TBC, and 21+80×BSA for the DA. The postoperative interval and age at examination were parameters associated with aortic size. We provide aortic areas in children and adolescents after correction of Tetralogy of Fallot measured by contrast-enhanced magnetic resonance angiography. Our 2D data may better depict the geometry of enlarged aortae than standard 1D diameters and serve as reference values for evaluating aortic disease in these patients.

Outcomes after Stereotactic Body Radiotherapy for Treatment of Hepatocellular Carcinoma

Stereotactic body radiotherapy (SBRT) is an effective treatment for hepatocellular carcinoma (HCC), especially for those cases whose location, size, or distance from major vessels preclude the use of other local modalities. This study was undertaken to report the outcomes of HCC after SBRT. We reviewed the treatment characteristics and outcomes of all patients with HCC treated with SBRT between December 2005 and December 2015 at our institution. SBRT doses were converted to biologically effective doses by using a standard linear quadratic model with an α/β ratio of 10 (BED10). Disease progression was analyzed by computed tomography (CT), using the modified Response Evaluation Criteria in Solid Tumors version 1.1 and by estimation of the area of viable tumor (contrast-enhanced areas on CT). Hepatobiliary toxicities (HBT) were graded according to the Common Terminology Criteria for Adverse Events v4.0. Time-to-events were calculated from date of SBRT. A total of 42 patients were included in this study. Median age was 65.5 years (range: 48-83). Liver cirrhosis was present in 26 (61.9%) patients, 23 (54.7%) were HCV-positive and 5 (11.9%) HBV-positive. By Child-Pugh (CP) liver function classification, 30 (71.4%) patients were class A and 12 (28.6%) class B. Median tumor size was 5.1 cm (range: 1.9-12). Thirty-eight (90.4%) patients received transarterial chemoembolization prior to SBRT, with a median interval of 76 days (range: 17-2627) prior to SBRT, while 4 (9.5%) received prior radiofrequency ablation. Median SBRT dose was 40 Gy (range: 22-50) delivered with a median of 5 fractions (range: 1-5). Median follow-up was 43 months (range: 5-143). Median overall survival (OS) was 25 months (14-37, 95% I.C.), with an OS of 76% at 1y and 51% at 2y. Accounting for competing risk of death, the cumulative incidence (CI) of local failure (LF) at 1 year was 17% and 21% at 2 years. The CI of failure within the liver outside the treated region was 55% at 1 year and 64% at 2 years, and the CI of distant failure was 25% at 1 and 2 years after SBRT. Patients treated with higher SBRT doses (BED10 ≥78 Gy, n=24) showed better median OS (37 vs. 14 months, P=0.004) compared to patients receiving lower SBRT doses. Tumor size did not correlate with local control or OS rates. The incidence of acute or late G3+ HBT was of 13% for CP A and and 25% for CP B (P=NS). The most common HBT was total bilirubin elevation at serum. Six (14%) patients presented a drop in CP class at 3 months after SBRT. No case of classic radiation induced liver disease was observed. This study confirms the efficacy of SBRT for the treatment of HCC, even for large tumors, and can be safely delivered with low rates of HBT, especially for patients with preserved liver function.