Contrast-enhancing Tumor Research Articles

Probabilistic independent component analysis of dynamic susceptibility contrast perfusion MRI in metastatic brain tumors

PurposeTo identify clinically relevant magnetic resonance imaging (MRI) features of different types of metastatic brain lesions, including standard anatomical, diffusion weighted imaging (DWI) and dynamic susceptibility contrast (DSC) perfusion MRI.MethodsMRI imaging was retrospectively assessed on one hundred and fourteen (N = 114) brain metastases including breast (n = 27), non-small cell lung cancer (NSCLC, n = 43) and ‘other’ primary tumors (n = 44). Based on 114 patient’s MRI scans, a total of 346 individual contrast enhancing tumors were manually segmented. In addition to tumor volume, apparent diffusion coefficients (ADC) and relative cerebral blood volume (rCBV) measurements, an independent component analysis (ICA) was performed with raw DSC data in order to assess arterio-venous components and the volume of overlap (AVOL) relative to tumor volume, as well as time to peak (TTP) of T2* signal from each component.ResultsResults suggests non-breast or non-NSCLC (‘other’) tumors had higher volume compare to breast and NSCLC patients (p = 0.0056 and p = 0.0003, respectively). No differences in median ADC or rCBV were observed across tumor types; however, breast and NSCLC tumors had a significantly higher “arterial” proportion of the tumor volume as indicated by ICA (p = 0.0062 and p = 0.0018, respectively), while a higher “venous” proportion were prominent in breast tumors compared with NSCLC (p = 0.0027) and ‘other’ lesions (p = 0.0011). The AVOL component was positively related to rCBV in all groups, but no correlation was found for arterial and venous components with respect to rCBV values. Median time to peak of arterial and venous components were 8.4 s and 12.6 s, respectively (p < 0.0001). No difference was found in arterial or venous TTP across groups.ConclusionsAdvanced ICA-derived component analysis demonstrates perfusion differences between metastatic brain tumor types that were not observable with classical ADC and rCBV measurements. These results highlight the complex relationship between brain tumor vasculature characteristics and the site of primary tumor diagnosis.

Evaluation of Skull Base Tumors with Dynamic TurboFLASH MRI during Gadolinium Injection.

Background and Purpose This study was aimed to investigate the role of dynamic TurboFLASH gadolinium (Gd) magnetic resonance (MR) imaging in improving the differential diagnosis of skull base tumors. Methods Eleven patients with skull base tumors underwent standard MR and ultrafast TurboFLASH sequence during gadolinium injection. Results The characterization of tumor vascularity was performed. Different patterns of gadolinium uptake for each tumor type were observed. This is particularly important to identify tumors at high risk of intraoperative bleeding. All glomus tumors, typically highly vascularized, showed an enhancement at the arterial phase, reflecting the arterialization of these tumors which is not detectable on conventional MR. No signal increase at the arterial phase was instead observed in other cases in which the ruling out of a glomus tumor was important because of the location of the lesion. Moreover TurboFLASH identified the pathognomonic "filling-in" profile of cavernous sinus cavernous hemangiomas (CSCH), that is, the progressive centripetal enhancement of the lesion at the beginning of the venous phase. Conclusion The dynamic analysis of tumor contrast enhancement with the TurboFLASH sequence provides useful additional information to that obtained with conventional MR, improving the differential diagnosis of skull base tumors, particularly in the distinction between glomus and nonglomus tumors and in diagnosing CSCH.

Results of Phosphorus Magnetic Resonance Spectroscopy for Brain Metastases Correlate with Histopathologic Results

Brain metastases (BMs) are classically well-circumscribed lesions. Still, the amount of edema in these neoplasms suggests either mechanisms of infiltration or defense. A better understanding of the mechanisms within the edema of BMs seems reasonable to preoperatively identify areas of potential infiltration and resect them. BMs represent tumors with high energy demand and cell turnover; therefore, they qualify for preoperative investigation with phosphorus-31 magnetic resonance spectroscopy (31PMRS), which reveals information about those characteristics. Ten patients with BMs were included in this trial. All underwent preoperative standard magnetic resonance imaging with additional 31PMRS. In all patients, 1 voxel within the contrast-enhancing tumor (CE+), 1 voxel at the border (including CE+ areas and surrounding T2-hyperintensive [T2+] areas), and 1 distant voxel purely including T2+ areas were determined by a neuroradiologist and a neurosurgeon. A frameless stereotactic biopsy was performed after craniotomy. Subsequently, the metabolites of the 31PMRS were analyzed and compared with the histopathologic results. Ratios, reflecting resynthesis (CE+/border/T2+: 1.109 ± 0.192/1.112 ± 0.158/1.083 ± 0.097), hydrolysis (0.303 ± 0.089/0.360 ± 0.122/0.321 ± 0.089), energy demand (4.227 ± 2.35/3.453 ± 1.284/3.599 ± 0.833), and membrane turnover (1.239 ± 0.2611/3.453 ± 1.284/3.599 ± 0.283) were calculated and compared intraindividually with a voxel from the contralateral side (resynthesis/hydrolysis/energy demand/membrane turnover: 1.063 ± 0.085/0.335 ± 0.073/3.317 ± 0.7573/0.784 ± 0.186), respectively. Resynthesis showed a trend toward higher ratios in CE+ and border biopsies without reaching statistical significances. This trend was also seen concerning energy demand. Membrane turnover was significantly higher in CE+, border zone, and also in the T2+ areas compared with controls (P > 0.001). 31PMRS in BMs provides information on metabolic changes in tumor and surrounding edema. There is proof of enhanced metabolism in tissue without histologic tumor manifestation.

Endoscopic Endonasal Excision of Large and Giant Pituitary Adenomas: Radiological and Intraoperative Correlates of the Extent of Resection

Despite the superb visualization offered by the endoscopic endonasal transsphenoidal approach, the resection rates of large and giant pituitary adenomas have remained much lower than those of smaller macroadenomas. Various tumor characteristics can influence the extent of resection (EOR) and have been variably reported. Additional understanding of these factors is mandatory to improve the results. We analyzed the radiological and intraoperative tumor characteristics influencing the EOR in a cohort of patients with large and giant pituitary macroadenomas undergoing endoscopic endonasal transsphenoidal excision under our care. Twenty-eight patients were included. Magnetic resonance images were retrospectively analyzed for pre- and postoperative tumor volumetric analysis; preoperative tumor volume calculation using the formula (A× B× C/2); preoperative radioanatomical characteristics, including tumor shape, radiological structure, contrast enhancement, and extension; and the EOR. Intraoperative data were retrieved and included. The preoperative calculated tumor volume was 38.14 ± 23.02 cm3 and the preoperative measured tumor volume was 50.345 ± 17.36 cm3. A statistically significant difference was found between the calculated and measured tumor volumes for the whole cohort and for tumors with a maximum diameter >3.9 cm. A statistically significant difference in the EOR was found at a volume threshold of 26.2 cm3. Large cysts, heterogeneous enhancement, Knosp grade ≤2, soft tumor consistency, and tumor hemorrhage were significantly associated with gross total resection. Volumetric analysis should replace 2-dimensional methods in determining the size of large and giant pituitary adenomas. Specific tumor characteristics were associated with the EOR and could help in predicting the EOR for these tumors.

A dual-purpose MRI acquisition to combine 4D-MRI and dynamic contrast-enhanced imaging for abdominal radiotherapy planning

For successful abdominal radiotherapy it is crucial to have a clear tumor definition and an accurate characterization of the motion. While dynamic contrast-enhanced (DCE) MRI aids tumor visualization, it is often hampered by motion artifacts. 4D-MRI characterizes this motion, but often lacks the contrast to clearly visualize the tumor. This dual requirement is challenging due to time constraints. Here, we propose combining both into a single acquisition by reconstructing the data in various ways in order to achieve both high spatio-temporal resolution DCE-MRI and accurate 4D-MRI motion estimates.A 5 min T1-weigthed DCE acquisition was collected in five renal-cell carcinoma patients and simulated in a digital phantom. Data were acquired continuously using a 3D golden angle radial stack-of-stars acquisition. This enabled three types of reconstruction; (1) a high spatio-temporal resolution DCE time series, (2) a 5D reconstruction and (3) a contrast-enhanced 4D-MRI for motion characterization. Motion extracted from the 4D- and 5D-MRI was compared with a separately acquired 4D-MRI and additional 2D cine MR imaging.Simulations on XCAT showed that 5D reconstructions severely underestimated motion (), whereas contrast-enhanced 4D-MRI only underestimated motion by . This was confirmed in the in vivo data where motion of the contrast-enhanced 4D-MRI was approximately smaller than the motion in the 2D cine MRI (5.8 mm versus 6.5 mm), but equal to a separately acquired 4D-MRI (5.8 mm versus 5.9 mm). 5D reconstructions underestimated the motion by more than , but minimized respiratory-induced blurring in the contrast enhanced images. DCE time-series demonstrated clear tumor visualization and contrast enhancement throughout the entire field-of-view.DCE- and 4D-MRI can be integrated into a single acquisition that enables different reconstructions with complementary information for abdominal radiotherapy planning and, in an MRI-guided treatment, precise motion information, input for motion models, and rapid feedback on the contrast enhancement.

Conventional Magnetic Resonance Features for Predicting 1p19q Codeletion Status of World Health Organization Grade II and III Diffuse Gliomas.

The conventional magnetic resonance features of World Health Organization (WHO) grade II and III diffuse gliomas in relation to chromosome 1p and 19q deletions (1p19q codeletion) were analyzed. We identified 147 cases of WHO grade II and III diffuse gliomas (1p/19q codeletion, 36 cases; no 1p/19q codeletion, 111 cases). χ Test and univariate and multivariate binary logistic regression analyses were conducted to evaluate the association between the imaging features and 1p19q codeletion status of WHO grade II and III diffuse gliomas in the discovery group, including the WHO grade II and III subgroups. (1) In the entire population, multivariate regression demonstrated that proportion contrast-enhanced tumor (>5% vs ≤5%; odds ratio [OR], 0.169; P = 0.009), enhancing margin (poorly vs well defined; OR, 12.435; P = 0.002), and hemorrhage (yes vs no; OR, 21.082; P < 0.001) were associated with a higher incidence of 1p19q codeletion status. The nomogram showed good discrimination (area under the curve [AUC], 0.803) and calibration. (2) For grade II tumors, subgroup analysis found that enhancing margin (poorly vs well defined; OR, 0.308; P = 0.007) and subventricular zone (presence vs absence-; OR, 0.137; P < 0.001) were associated with a higher incidence of 1p19q codeletion status (AUC, 0.779). (3) For grade III tumors, subgroup analysis found that age (≥40 years vs <40 years; OR, 5.977; P = 0.03) and hemorrhage (yes vs no; OR, 18.051; P < 0.001) were associated with a higher incidence of 1p19q codeletion status (AUC, 0.816). Conventional magnetic resonance features can be conveniently used to facilitate the preoperative prediction of 1p19q codeletion status of WHO grade II and III diffuse gliomas. Decision curve analysis demonstrated that the nomogram was clinically useful.

PH-weighted amine chemical exchange saturation transfer echoplanar imaging (CEST-EPI) as a potential early biomarker for bevacizumab failure in recurrent glioblastoma.

The objective of the current study was to explore the efficacy of using pH-weighted amine CEST-EPI as a potential non-invasive imaging biomarker for treatment response and/or failure in recurrent GBM patients treated with bevacizumab. A total of 11 patients with recurrent GBM treated with bevacizumab were included in this prospective study. CEST-EPI, perfusion MRI, and standardized anatomic MRI were obtained in patients before and after bevacizumab administration. CEST-EPI measures of magnetization transfer ratio asymmetry (MTRasym) at 3ppm were used for pH-weighted imaging contrast. Multiple measures were examined for their association with progression-free survival (PFS). Tumor acidity, measured with MTRasym at 3ppm, was significantly reduced in both contrast enhancing and non-enhancing tumor after bevacizumab (p = 0.0002 and p < 0.00001, respectively). The reduction in tumor acidity in both contrast enhancing and non-enhancing tumor was linearly correlated with PFS (p = 0.044 and p = 0.00026, respectively). In 9 of the 11 patients, areas of residual acidity were localized to areas of tumor recurrence, typically around 2 months prior to radiographic progression. Univariate (p = 0.006) and multivariate Cox regression controlling for age (p = 0.009) both indicated that change in tumor acidity (ΔMTRasym at 3ppm) was a significant predictor of PFS. This pilot study suggests pH-weighted amine CEST MRI may have value as a non-invasive, early imaging biomarker for bevacizumab treatment response and failure. Early decreases MTRasym at 3.0ppm in recurrent GBM after bevacizumab may be associated with better PFS. Residual or emerging regions of acidity may colocalize to the site of tumor recurrence.

Role of postoperative tumor volume in patients with MGMT-unmethylated glioblastoma.

The aim of this study is to investigate the association between postoperative tumor volume and overall survival (OS) of O6-methylguanine DNA methyltransferase (MGMT)-unmethylated glioblastoma patients. One hundred-twenty-six patients with MGMT-unmethylated glioblastoma who were treated either with surgical resection or needle biopsy between 2006 and 2015 were included in this retrospective cohort. Pre- and postcontrast T1 weighted images were evaluated in order to determine pre- and postoperative contrast-enhancing tumor volumes (CE-TV). Cox regression models adjusted for other significant prognostic factors were used to investigate the association between postoperative tumor volume and survival. Complete resection of CE-TV was significantly associated with longer OS in the univariate analysis (HR 0.61; 95% CI 0.40-0.94; p = 0.02). However, this fact could not be confirmed after adjusting the model for other relevant prognostic factors (HR 1.01; 95% CI 0.65-1.55; p = 0.962). Postoperative CE-TV was significantly associated with survival in both univariate (HR: 1.04; 95% CI 1.025-1.055; p < 0.001) and multivariate analyses (HR: 1.027; 95% CI 1.005-1.049; p = 0.014). Although complete resection of tumor tissue was not significantly associated with longer OS in MGMT-unmethylated GBM patients, maximum safe resection should always be attempted, since postoperative tumor volume is strongly associated with OS.

Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents

PurposeTo quantitate gadolinium deposits in gliomas and adjacent normal brain specimens, and to evaluate their association with tumor contrast enhancement and the type of gadolinium-based contrast agent (GBCA) used.MethodsA total of 69 patients with primary glioma who underwent contrast-enhanced magnetic resonance imaging (MRI) prior to surgery were included in this retrospective study. Gadolinium was measured from histologically viable tumor, normal brain, and necrosis within the sample, when available, using inductively coupled plasma mass spectrometry (ICP-MS). Tumor contrast enhancement was categorized as none, minimal, or noticeable. Differences in gadolinium deposits by contrast enhancement and GBCA type were assessed.ResultsSeven patients received linear GBCA and 62 macrocyclic, respectively. At the time of surgery, gadolinium deposits were detected in 39 out of 69 (57%) tumor samples, 8 out of 13 (62%) normal brain, and 12 out of 14 (86%) necrotic specimens. Gadolinium was detected in both enhancing and non-enhancing tumors, but was greatest in gliomas with noticeable enhancement (p = 0.02). Administration of linear agents gadodiamide and gadopentetate dimeglumine resulted in significantly higher tumor gadolinium relative to macrocyclic gadoterate meglumine (p < 0.01 and p < 0.05, respectively). Normal brain and necrosis also showed higher gadolinium after exposure to linear gadodiamide (both p < 0.05). In multivariate regression, GBCA type (linear/macrocyclic) was the most powerful predictor of tumor gadolinium retention (p < 0.001).ConclusionGadolinium can be detected in both enhancing and non-enhancing gliomas, neighboring normal brain, and necrosis. Gadolinium retention is higher after exposure to linear GBCAs compared with the macrocyclic gadoterate meglumine.

Differentiation of hypovascular pancreatic neuroendocrine tumors from pancreatic ductal adenocarcinoma using contrast-enhanced computed tomography.

Hypovascular pancreatic neuroendocrine tumors (hypo-PNETs) are often misdiagnosed as pancreatic ductal adenocarcinoma (PDAC). However, the treatment options and prognosis of PNETs and PDAC are substantially different. This retrospective study differentiated hypo-PNETs from PDAC using contrast-enhanced CT (CE-CT). Clinical data and CE-CT findings, including tumor location, size, boundary, pancreatic duct dilatation, local invasion or metastases, tumor contrast enhancement, and tumor-to-pancreas enhancement ratio, were compared between 39 PDACs and 18 hypo-PNETs. At CT imaging, hypo-PNETs showed a higher frequency of a well-defined margin and lower frequencies of pancreatic duct dilatation and local invasion or metastasis when compared with PDAC (p < 0.05 for all). The mean attenuation of hypo-PNETs at the arterial and portal venous phase was significantly higher than that of PDAC (p < 0.001, p = 0.003, respectively). Similar results were observed in tumor-to-pancreas enhancement ratio. Tumor attenuation and tumor-to-pancreas enhancement ratio at the arterial phase showed the largest area under the curve (AUC) of 0.888 and 0.812 with 83.3–88.9% of sensitivity and 61.6–77.0% of specificity. Pancreatic duct dilatation, local invasion or metastasis, and tumor attenuation at the portal venous phase also showed acceptable AUC (0.703–0.748). Thus CE-CT features, especially the enhancement degree at the arterial phases, may be useful for differentiating hypo-PNETs from PDAC using CE-CT.

Multi-parametric and multi-regional histogram analysis of MRI: modality integration reveals imaging phenotypes of glioblastoma

ObjectivesIntegrating multiple imaging modalities is crucial for MRI data interpretation. The purpose of this study is to determine whether a previously proposed multi-view approach can effectively integrate the histogram features from multi-parametric MRI and whether the selected features can offer incremental prognostic values over clinical variables.MethodsEighty newly-diagnosed glioblastoma patients underwent surgery and chemoradiotherapy. Histogram features of diffusion and perfusion imaging were extracted from contrast-enhancing (CE) and non-enhancing (NE) regions independently. An unsupervised patient clustering was performed by the multi-view approach. Kaplan-Meier and Cox proportional hazards regression analyses were performed to evaluate the relevance of patient clustering to survival. The metabolic signatures of patient clusters were compared using multi-voxel spectroscopy analysis. The prognostic values of histogram features were evaluated by survival and ROC curve analyses.ResultsTwo patient clusters were generated, consisting of 53 and 27 patients respectively. Cluster 2 demonstrated better overall survival (OS) (p = 0.007) and progression-free survival (PFS) (p < 0.001) than Cluster 1. Cluster 2 displayed lower N-acetylaspartate/creatine ratio in NE region (p = 0.040). A higher mean value of anisotropic diffusion in NE region was associated with worse OS (hazard ratio [HR] = 1.40, p = 0.020) and PFS (HR = 1.36, p = 0.031). The seven features selected by this approach showed significantly incremental value in predicting 12-month OS (p = 0.020) and PFS (p = 0.022).ConclusionsThe multi-view clustering method can provide an effective integration of multi-parametric MRI. The histogram features selected may be used as potential prognostic markers.Key Points• Multi-parametric magnetic resonance imaging captures multi-faceted tumor physiology.• Contrast-enhancing and non-enhancing tumor regions represent different tumor components with distinct clinical relevance.• Multi-view data analysis offers a method which can effectively select and integrate multi-parametric and multi-regional imaging features.

Low perfusion compartments in glioblastoma quantified by advanced magnetic resonance imaging and correlated with patient survival

Background and purposeGlioblastoma exhibits profound intratumoral heterogeneity in perfusion. Particularly, low perfusion may induce treatment resistance. Thus, imaging approaches that define low perfusion compartments are crucial for clinical management. Materials and methodsA total of 112 newly diagnosed glioblastoma patients were prospectively recruited for maximal safe resection. The apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV) were calculated from diffusion and perfusion imaging, respectively. Based on the overlapping regions of lowest rCBV quartile (rCBVL) with the lowest ADC quartile (ADCL) and highest ADC quartile (ADCH) in each tumor, two low perfusion compartments (ADCH-rCBVL and ADCL-rCBVL) were identified for volumetric analysis. Lactate and macromolecule/lipid levels were determined from multivoxel MR spectroscopic imaging. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan–Meier’s and multivariate Cox regression analyses, to evaluate the effects of compartment volume and lactate level on survival. ResultsTwo compartments displayed higher lactate and macromolecule/lipid levels compared to contralateral normal-appearing white matter (each P < 0.001). The proportion of the ADCL-rCBVL compartment in the contrast-enhancing tumor was associated with a larger infiltration on FLAIR (P < 0.001, rho = 0.42). The minimally invasive phenotype displayed a lower proportion of the ADCL-rCBVL compartment than the localized (P = 0.031) and diffuse phenotypes (not significant). Multivariate Cox regression showed higher lactate level in the ADCL-rCBVL compartment was associated with worsened survival (PFS: HR 2.995, P = 0.047; OS: HR 4.974, P = 0.005). ConclusionsOur results suggest that the ADCL-rCBVL compartment may potentially indicate a clinically measurable resistant compartment.

Acoustic protein nanostructures for contrast ultrasound

Gas vesicles (GVs) are nanosized protein-encased gas particles produced in species of Bacteria and Archea. Similar to microbubbles, GVs can generate harmonic signals when exposed to ultrasound, making it an alternative agent for contrast imaging. In addition, their protein shell allows for continuous gas exchange with the environment resulting in a physically stable long-lasting structure. A further advantage of gas vesicles is their size (40-500 nm), which has the potential for extravasation out of leaky vasculatures of tumors. This can potentially allow for targeting molecular biomarkers outside of the vasculature. Using the Vevo®2100 system (FUJIFILM VisualSonics, Toronto, Canada) operating at 18MHz, we imaged mouse tumor models to optimize and improve signal enhancement. GVs were isolated and purified from Halobacterium sp. NRC-1 and quantified using the optical density at 500nm (OD500). Mouse tumor models were generated using Lewis Lung Carcinoma cells injected into SHO mice and imaged after 14 days. A total of 300 µL of GVs at a concentration of 40 OD500 was injected intravenously at an infusion rate of 500 µL/min. Non-linear contrast enhancement in tumors was clearly visible after infusion of GVs, with wash-in curves showing high SNR. Unfortunately, in contrast to the liver where a prolong enhancement was observed, a rapid loss of contrast was seen in tumors post-injection. Inhibition of the RES is a well-known method to improve circulation of nanosized particles. The saturation of liver Kupffer cells using a double injection showed better signal retention (40-70%) increase following the second administration of GVs, in comparison to the first. Additionally, the disruption of Kupffer cell function using either GdCl3 or Intralipid also resulted in prolonged signal retention. To examine a more biocompatible method of blocking GVs detection by the RES, the surface of GVs were modified with the addition of PEG chains of varying lengths. A 5 kDa PEG length showed 75% signal retention during the washout phase of contrast enhancement.

INITIAL RESULTS IN RECURRENT BRAIN GLIOBLASTOMAS MANAGEMENT WITH MAXIMAL SAFE RESECTION FOLLOWED BY INTAOPERATIVE BALLOON ELECTRONIC BRACHYTERAPY

Brain glioblastomas (GBM) are notorious for their early local recurrence despite of standard combined treatment. Technologies for recurrent GBM management require further development and research. Resection of malignant gliomas must be followed by an adjuvant treatment. Intraoperative balloon electronic brachytherapy (IBEB) has been recently introduced into clinical practice and could be successfully applied to recurrent GBM management. This article presents the initial results of recurrent GBM management with maximal safe resection followed by IBEB. Material and methods . Patients (n = 11) with recurrent GBM after standard combined treatment were managed with maximal safe microsurgical resection followed by IBEB. The follow-up period after IBEB ranged from 1 to 30 months. Results. The median overall survival for the entire study group of patients included in the statistical analysis (n = 9) was 27 months (range 17–47 months). In the subgroup of patients (n = 4) with contrast-enhanced tumor MRI volume after resection ≤ 2.5 cm3, the median local progression free survival (locPFS) was 21.25 months (range 10–30 months). Conclusion. Initial results in recurrent brain GBMs management with resection followed by IBEB seems to be promising, especially in case of contrast-enhanced tumor volume detected on MRI after resection is less than 2.5 cm3 without signs of multifocal tumor growth.

The mediating role of extent of resection in the relationship between the tumor characteristics and survival outcome of glioma.

The prognostic value of tumor characteristics for glioma has been controversial, partly because of a lack of knowledge about how these associations develop. Extent of resection may be factors that mediate the relationship between tumor characteristics and the hazard of death from glioma.Patients and Methods: This consecutive study retrospectively included a group of 393 treatment-naive patients with newly, pathologically confirmed glioma between January 2004 and December 2014. Information on patient age, gender, Karnofsky Performance Status (KPS), tumor grade, tumor size, tumor location, presence or absence of contrast enhancement on MRI and extent of tumor resection have all been collected. The discrete-time survival model integrating survival outcomes within structural equation models was employed to develop and evaluate a comprehensive hypothesis regarding the direct and indirect impact of tumor characteristics on the hazard of death from glioma, mediated by the extent of resection.Results: Except for tumor location, the indirect effects of tumor grade, contrast enhancement, and tumor size on PFS of glioma through extent of resection were found significant in the model.Conclusion: This study provides a better understanding of the process through which tumor characteristics is associated with hazard of death from glioma.

Multimodal Imaging of Nonenhancing Glioblastoma Regions.

Background:Clinical glioblastoma treatment mostly focuses on the contrast-enhancing tumor mass. Amino acid positron emission tomography (PET) can detect additional, nonenhancing glioblastoma-infiltrated brain regions that are difficult to distinguish on conventional magnetic resonance imaging (MRI). We combined MRI with perfusion imaging and amino acid PET to evaluate such nonenhancing glioblastoma regions.Methods:Structural MRI, relative cerebral blood volume (rCBV) maps from perfusion MRI, and α-[11C]-methyl-l-tryptophan (AMT)-PET images were analyzed in 20 patients with glioblastoma. The AMT uptake and rCBV (expressed as tumor to normal [T/N] ratios) were compared in nonenhancing tumor portions showing increased signal on T2/fluid-attenuated inversion recovery (T2/FLAIR) images.Results:Thirteen (65%) tumors showed robust heterogeneity in nonenhancing T2/FLAIR hyperintense areas on AMT-PET, whereas the nonenhancing regions in the remaining 7 cases had homogeneous AMT uptake (low in 6, high in 1). AMT and rCBV T/N ratios showed only a moderate correlation in the nonenhancing regions (r = 0.41, P = .017), but regions with very low rCBV (<0.79 T/N ratio) had invariably low AMT uptake.Conclusions:The findings demonstrate the metabolic and perfusion heterogeneity of nonenhancing T2/FLAIR hyperintense glioblastoma regions. Amino acid PET imaging of such regions can detect glioma-infiltrated brain for treatment targeting; however, very low rCBV values outside the contrast-enhancing tumor mass make increased AMT uptake in nonenhancing glioblastoma regions unlikely.

Quantitative histopathologic assessment of perfusion MRI as a marker of glioblastoma cell infiltration in and beyond the peritumoral edema region.

Conventional MRI fails to detect regions of glioblastoma cell infiltration beyond the contrast-enhanced T1 solid tumor region, with infiltrating tumor cells often migrating along host blood vessels. To quantitatively and qualitatively analyze the correlation between perfusion MRI signal and tumor cell density in order to assess whether local perfusion perturbation could provide a useful biomarker of glioblastoma cell infiltration. Animal model. Mice bearing orthotopic glioblastoma xenografts generated from a patient-derived glioblastoma cell line. 7T perfusion images acquired using a high signal-to-noise ratio (SNR) multiple boli arterial spin labeling sequence were compared with conventional MRI (T1 /T2 weighted, contrast-enhanced T1 , diffusion-weighted, and apparent diffusion coefficient). Immunohistochemistry sections were stained for human leukocyte antigen (probing human-derived tumor cells). To achieve quantitative MRI-tissue comparison, multiple histological slices cut in the MRI plane were stacked to produce tumor cell density maps acting as a "ground truth." Sensitivity, specificity, accuracy, and Dice similarity indices were calculated and a two-tailed, paired t-test used for statistical analysis. High comparison test results (Dice 0.62-0.72, Accuracy 0.86-0.88, Sensitivity 0.51-0.7, and Specificity 0.92-0.97) indicate a good segmentation for all imaging modalities and highlight the quality of the MRI tissue assessment protocol. Perfusion imaging exhibits higher sensitivity (0.7) than conventional MRI (0.51-0.61). MRI/histology voxel-to-voxel comparison revealed a negative correlation between tumor cell infiltration and perfusion at the tumor margins (P = 0.0004). These results demonstrate the ability of perfusion imaging to probe regions of low tumor cell infiltration while confirming the sensitivity limitations of conventional imaging modalities. The quantitative relationship between tumor cell density and perfusion identified in and beyond the edematous T2 hyperintensity region surrounding macroscopic tumor could be used to detect marginal tumor cell infiltration with greater accuracy. 1 Technical stage: 2 J. Magn. Reson. Imaging 2019;50:529-540.

Wavelet-based reconstruction of dynamic susceptibility MR-perfusion: a new method to visualize hypervascular brain tumors.

Parameter maps based on wavelet-transform post-processing of dynamic perfusion data offer an innovative way of visualizing blood vessels in a fully automated, user-independent way. The aims of this study were (i) a proof of concept regarding wavelet-based analysis of dynamic susceptibility contrast (DSC) MRI data and (ii) to demonstrate advantages of wavelet-based measures compared to standard cerebral blood volume (CBV) maps in patients with the initial diagnosis of glioblastoma (GBM). Consecutive 3-T DSC MRI datasets of 46 subjects with GBM (mean age 63.0 ± 13.1years, 28 m) were retrospectively included in this feasibility study. Vessel-specific wavelet magnetic resonance perfusion (wavelet-MRP) maps were calculated using the wavelet transform (Paul wavelet, order 1) of each voxel time course. Five different aspects of image quality and tumor delineation were each qualitatively rated on a 5-point Likert scale. Quantitative analysis included image contrast and contrast-to-noise ratio. Vessel-specific wavelet-MRP maps could be calculated within a mean time of 2:27min. Wavelet-MRP achieved higher scores compared to CBV in all qualitative ratings: tumor depiction (4.02 vs. 2.33), contrast enhancement (3.93 vs. 2.23), central necrosis (3.86 vs. 2.40), morphologic correlation (3.87 vs. 2.24), and overall impression (4.00 vs. 2.41); all p < .001. Quantitative image analysis showed a better image contrast and higher contrast-to-noise ratios for wavelet-MRP compared to conventional perfusion maps (all p < .001). wavelet-MRP is a fast and fully automated post-processing technique that yields reproducible perfusion maps with a clearer vascular depiction of GBM compared to standard CBV maps. • Wavelet-MRP offers high-contrast perfusion maps with a clear delineation of focal perfusion alterations. • Both image contrast and visual image quality were beneficial for wavelet-MRP compared to standard perfusion maps like CBV. • Wavelet-MRP can be automatically calculated from existing dynamic susceptibility contrast (DSC) perfusion data.

Radiographic assessment of contrast enhancement and T2/FLAIR mismatch sign in lower grade gliomas: correlation with molecular groups.

With the updated World Health Organization (WHO) 2016 neuropathological diagnostic criteria, radiographic prognostic associations in lower-grade gliomas (LGG, WHO grade II and III) are undergoing re-evaluation. We identified 316 LGG patients (151 grade II and 165 grade III) for a combined cohort from three independent databases. We analyzed the preoperative axial FLAIR, axial T2-weighted and post-gadolinium volumetric T1-weighted MR images. The molecular data collected included the status of IDH1/2, TP53, TERT promoter and ATRX mutations, in addition to 1p/19q co-deletions. In a subset of cases (n = 133), we assessed the "T2-FLAIR mismatch" sign. Gliomas were assigned to one of the three molecular groups: Group O (IDH-mutant, 1p/19q co-deleted oligodendrogliomas, n = 95), Group A (IDH-mutant, ATRX inactivated astrocytomas, n = 175) and Group G (IDH wild-type, GBM-like, n = 46). A contrast-enhancing tumor was seen in 98 patients (31%), most frequently in Group G (n = 28/45, 57%), when compared to Group A (n = 49/175, 28%) and Group O (n = 24/95, 25.3%) tumors (p = 0.008 and p = 0.0011, respectively). Consistent with previous reports, T2-FLAIR mismatch was preferentially found in Group A tumors (73.1%, 60 of 82), although its presence was not associated with survival, after controlling for molecular group. False positive mismatch sign was noted in 28.5% (12/42) Group O tumors, but none of the tumors in Group G. A combination of all three factors: age under 40years at first diagnosis, a tumor size larger than 6cm and T2-FLAIR mismatch was highly specific for IDH mutant astrocytoma (Group A). We identify radiographic correlates of molecular groups in lower-grade gliomas, which join clinical demographic features in defining the characteristic presentation of these tumors. Radiographic correlates of prognosis in LGG require re-evaluation within molecular group.

Computed tomographic contrast enhancement and tumor angiogenesis in canine oral tumors

Computed tomographic contrast enhancement and tumor angiogenesis in canine oral tumors