scholarly journals Quantitation of brain tumour microstructure response to Temozolomide therapy using non-invasive VERDICT MRI

2017 ◽  
Author(s):  
Tom A. Roberts ◽  
Harpreet Hyare ◽  
Giulia Agliardi ◽  
Ben Hipwell ◽  
Angela d’Esposito ◽  
...  
Keyword(s):  
Treatment Response ◽  
Volume Fraction ◽  
Imaging Techniques ◽  
Structural Mri ◽  
Low Grade ◽  
Human Gliomas ◽  
Cell Radius ◽  
Apparent Diffusion ◽  
Dimensional Measurements ◽  
Intracellular Volume

ABSTRACTThere has been slow progress in the development of new therapeutic strategies for treating brain tumours, partly because assessment of treatment response is difficult and largely reliant on simple bi-dimensional measurements of MRI contrast-enhancing regions. Hence, there is a clinical need to develop improved imaging techniques for monitoring treatment response. In this study, we evaluate VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) MRI in mouse glioblastomas for the quantification of tumour microstructure and assessment of response to Temozolomide (TMZ) chemotherapy, and, we investigate the feasibility of applying VERDICT MRI in a range of human gliomas. VERDICT MRI detected response to TMZ earlier than structural and apparent diffusion coefficient (ADC) measurements. A significant reduction in the cell radius parameter was detected three days earlier than ADC and six days earlier than structural MRI. Histological analysis showed the same trend as VERDICT of decreased intracellular volume fraction in the TMZ-treated mice. Vascular volume fraction was not altered by TMZ, which was consistent with optical projection tomography measurements. In patients, glioblastoma compartmental volume fractions showed good agreement with mouse glioblastoma parameters. The VERDICT parameters varied across the human gliomas, with raised intracellular volume fraction in the oligodendrogliomas and elevated cell radius in both low-grade tumours subtypes. In conclusion, our results suggest that VERDICT MRI is more sensitive at detecting TMZ response than structural or ADC measurements. In patients, VERDICT is feasible within clinical scan times, and performed best at characterising glioblastoma. Further optimisation should improve assessment of different glioma subtypes.

scholarly journals VERDICT MRI for Prostate Cancer: Intracellular Volume Fraction versus Apparent Diffusion Coefficient

Radiology ◽  
2019 ◽  
Vol 291 (2) ◽  
pp. 391-397 ◽  
Author(s):  
Edward W. Johnston ◽  
Elisenda Bonet-Carne ◽  
Uran Ferizi ◽  
Ben Yvernault ◽  
Hayley Pye ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Volume Fraction ◽  
Apparent Diffusion ◽  
Fraction Versus ◽  
Intracellular Volume

scholarly journals TAMI-08. A TALE OF TWO TELOMERE MAINTENANCE MECHANISMS: TERT EXPRESSION AND THE ALT PATHWAY INDUCE UNIQUE MRS-DETECTABLE METABOLIC REPROGRAMMING IN LOW-GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii214-ii214
Author(s):  
Pavithra Viswanath ◽  
Georgios Batsios ◽  
Anne Marie Gillespie ◽  
Hema Artee Luchman ◽  
Joseph Costello ◽  
...  
Keyword(s):  
Treatment Response ◽  
Metabolic Reprogramming ◽  
Telomere Maintenance ◽  
Imaging Biomarker ◽  
Low Grade ◽  
Tumor Proliferation ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Non Invasive ◽  
Key Enzyme ◽  
Tert Expression

Abstract Telomeres are nucleoprotein structures at chromosomal ends that shorten with cell division and constitute a natural barrier to proliferation. In order to proliferate indefinitely, all tumors require a telomere maintenance mechanism (TMM). Telomerase reverse transcriptase (TERT) expression is the TMM in most tumors, including low-grade oligodendrogliomas (LGOGs). In contrast, low-grade astrocytomas (LGAs) use the alternative lengthening of telomeres (ALT) pathway as their TMM. As molecular hallmarks of tumor proliferation, TMMs are attractive tumor biomarkers and therapeutic targets. Non-invasive imaging of TMM status will, therefore, allow assessment of tumor proliferation and treatment response. However, translational methods of imaging TMM status are lacking. Here, we show that TERT expression and the ALT pathway are associated with unique magnetic resonance spectroscopy (MRS)-detectable metabolic reprogramming in LGOGs and LGAs respectively. In genetically-engineered and patient-derived LGOG models, TERT expression is linked to elevated 1H-MRS-detectable NAD(P)/H, glutathione, aspartate and AXP. In contrast, the ALT pathway in LGAs is associated with higher α-ketoglutarate, glutamate, alanine and AXP. Importantly, elevated flux of hyperpolarized [1-13C]-alanine to pyruvate, which depends on α-ketoglutarate, is a non-invasive in vivo imaging biomarker of the ALT pathway in LGAs while elevated flux of hyperpolarized [1-13C]-alanine to lactate, which depends on NADH, is an imaging biomarker of TERT expression in LGOGs. Mechanistically, the ALT pathway in LGAs is linked to higher glutaminase (GLS), a key enzyme for α-ketoglutarate biosynthesis while TERT expression in LGOGs is associated with elevated nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme for NADH biosynthesis. Notably, TERT expression and the ALT pathway are linked to MRS-detectable metabolic reprogramming in LGOG and LGA patient biopsies, emphasizing the clinical validity of our observations. Collectively, we have identified unique metabolic signatures of TMM status that integrate critical oncogenic information with noninvasive imaging modalities that can improve diagnosis and treatment response monitoring for LGOG and LGA patients.

scholarly journals BIMG-04. MAPPING HETEROGENEITY OF HIGH-GRADE GLIOMA METABOLISM USING HIGH RESOLUTION 7T MRSI

2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i1-i1
Author(s):  
Gilbert Hangel ◽  
Cornelius Cadrien ◽  
Philipp Lazen ◽  
Sukrit Sharma ◽  
Julia Furtner ◽  
...  
Keyword(s):  
High Resolution ◽  
Imaging Techniques ◽  
Basis Set ◽  
Metabolic Imaging ◽  
Tumor Segmentation ◽  
Low Grade ◽  
High Grade ◽  
Isotropic Resolution ◽  
Contrast Enhanced ◽  
Definition Of

Abstract OBJECTIVES Neurosurgical resection in gliomas depends on the precise preoperative definition of the tumor and its margins to realize a safe maximum resection that translates into a better patient outcome. New metabolic imaging techniques could improve this delineation as well as designate targets for biopsies. We validated the performance of our fast high-resolution whole-brain 3D-magnetic resonance spectroscopic imaging (MRSI) method at 7T in high-grade gliomas (HGGs) as first step to this regard. METHODS We measured 23 patients with HGGs at 7T with MRSI covering the whole cerebrum with 3.4mm isotropic resolution in 15 min. Quantification used a basis-set of 17 neurochemical components. They were evaluated for their reliability/quality and compared to neuroradiologically segmented tumor regions-of-interest (necrosis, contrast-enhanced, non-contrast-enhanced+edema, peritumoral) and histopathology (e.g., grade, IDH-status). RESULTS We found 18/23 measurements to be usable and ten neurochemicals quantified with acceptable quality. The most common denominators were increases of glutamine, glycine, and total choline as well as decreases of N-acetyl-aspartate and total creatine over most tumor regions. Other metabolites like taurine and serine showed mixed behavior. We further found that heterogeneity in the metabolic images often continued into the peritumoral region. While 2-hydroxy-glutarate could not be satisfyingly quantified, we found a tendency for a decrease of glutamate in IDH1-mutant HGGs. DISCUSSION Our findings corresponded well to clinical tumor segmentation but were more heterogeneous and often extended into the peritumoral region. Our results corresponded to previous knowledge, but with previously not feasible resolution. Apart from glycine/glutamine and their role in glioma progression, more research on the connection of glutamate and others to specific mutations is necessary. The addition of low-grade gliomas and statistical ROI analysis in a larger cohort will be the next important steps to define the benefits of our 7T MRSI approach for the definition of spatial metabolic tumor profiles.

scholarly journals Low-Grade Gliomas: Six-month Tumor Growth Predicts Patient Outcome Better than Admission Tumor Volume, Relative Cerebral Blood Volume, and Apparent Diffusion Coefficient

Radiology ◽  
2009 ◽  
Vol 253 (2) ◽  
pp. 505-512 ◽  
Author(s):  
Gisele Brasil Caseiras ◽  
Olga Ciccarelli ◽  
Daniel R. Altmann ◽  
Christopher E. Benton ◽  
Daniel J. Tozer ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Diffusion Coefficient ◽  
Apparent Diffusion Coefficient ◽  
Tumor Growth ◽  
Blood Volume ◽  
Cerebral Blood Volume ◽  
Tumor Volume ◽  
Low Grade ◽  
Apparent Diffusion ◽  
Better Than

scholarly journals The Clinical Value of PET with Amino Acid Tracers for Gliomas WHO Grade II

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Anja Smits ◽  
Brigitta G. Baumert
Keyword(s):  
Amino Acid ◽  
Hot Spot ◽  
Imaging Techniques ◽  
Biological Behavior ◽  
Optimal Timing ◽  
Low Grade ◽  
Clinical Value ◽  
Who Grade ◽  
Positron Emission ◽  
Therapeutic Procedures

The clinical management of adults with low-grade gliomas (LGGs) remains a challenge. There is no curative treatment, and management of individual patients is a matter of deciding optimal timing as well as right treatment modality. In addition to conventional imaging techniques, positron emission tomography (PET) with amino acid tracers can facilitate diagnostic and therapeutic procedures. In this paper, the clinical applications of PET with amino acid tracers 11C-methyl-L-methionine (MET) and 18F-fluoro-ethyl-L-tyrosine (FET) for patients with LGG are summarized. We also discuss the value of PET for the long-term followup of this patient group. Monitoring metabolic activity by PET in individual patients during course of disease will provide insight in the biological behavior and evolution of these tumors. As such, spatial changes in tumor activity over time, including shifts of hot-spot regions within the tumor, may reflect intratumoral heterogeneity and correlate to clinical parameters.

scholarly journals IMG-07. GADOLINIUM IS NOT NECESSARY FOR SURVEILLANCE MR IMAGING IN CHILDREN WITH CHIASMATIC-HYPOTHALAMIC LOW GRADE GLIOMA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii356-iii356
Author(s):  
Fatema Malbari ◽  
Murali Chintagumpala ◽  
Jack Su ◽  
Mehmet Okcu ◽  
Frank Lin ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Three Dimensional ◽  
Low Grade Glioma ◽  
Cancer Center ◽  
Low Grade ◽  
Contrast Imaging ◽  
Post Contrast ◽  
Best Response ◽  
Dimensional Measurements ◽  
Initiation Of Therapy

Abstract BACKGROUND Patients with chiasmatic-hypothalamic low grade glioma (CHLGG) have frequent MRIs with gadolinium based contrast agents (GBCA) for disease monitoring. Cumulative gadolinium deposition in children is a potential concern. The purpose of this research is to establish whether MRI with GBCA is necessary for determining tumor progression in children with CHLGG. METHODS Children with progressive CHLGG were identified from Texas Children’s Cancer Center between 2005–2019. Pre- and post-contrast MRI sequences were separately reviewed by one neuroradiologist who was blinded to the clinical course. Three dimensional measurements and tumor characteristics were collected. Radiographic progression was defined as a 25% increase in size (product of two largest dimensions) compared to baseline or best response after initiation of therapy. RESULTS A total of 28 patients with progressive CHLGG including 683 MRIs with GBCA (mean 24 MRIs/patient; range: 10–43 MRIs) were reviewed. No patients had a diagnosis of NF1. Progression was observed 92 times, 91 (98.9%) on noncontrast and 90 (97.8%) on contrast imaging. Sixty-seven radiographic and/or clinical progressions necessitating management changes were identified in all (100%) noncontrast sequences and 66 (98.5%) contrast sequences. Tumor growth >2 mm in any dimension was identified in 184/187(98.4%) on noncontrast and 181/187(96.8%) with contrast imaging. Non primary metastatic disease was seen in seven patients (25%), which were better visualized on contrast imaging in 4 (57%). CONCLUSION MRI without GBCA effectively identifies patients with progressive disease. One should consider eliminating contrast in imaging of children with CHLGG with GBCA reserved for monitoring those with metastatic disease.

scholarly journals Imaging and Molecular Mechanisms of Alzheimer’s Disease: A Review

2018 ◽  
Vol 19 (12) ◽  
pp. 3702 ◽  
Author(s):  
Grazia Femminella ◽  
Tony Thayanandan ◽  
Valeria Calsolaro ◽  
Klara Komici ◽  
Giuseppe Rengo ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Multimodal Imaging ◽  
Molecular Mechanisms ◽  
Imaging Techniques ◽  
Structural Mri ◽  
Imaging Biomarkers ◽  
Significant Burden ◽  
Made In

Alzheimer’s disease is the most common form of dementia and is a significant burden for affected patients, carers, and health systems. Great advances have been made in understanding its pathophysiology, to a point that we are moving from a purely clinical diagnosis to a biological one based on the use of biomarkers. Among those, imaging biomarkers are invaluable in Alzheimer’s, as they provide an in vivo window to the pathological processes occurring in Alzheimer’s brain. While some imaging techniques are still under evaluation in the research setting, some have reached widespread clinical use. In this review, we provide an overview of the most commonly used imaging biomarkers in Alzheimer’s disease, from molecular PET imaging to structural MRI, emphasising the concept that multimodal imaging would likely prove to be the optimal tool in the future of Alzheimer’s research and clinical practice.

scholarly journals Immuno-Imaging to Predict Treatment Response in Infection, Inflammation and Oncology

2019 ◽  
Vol 8 (5) ◽  
pp. 681 ◽  
Author(s):  
Alberto Signore ◽  
Chiara Lauri ◽  
Sveva Auletta ◽  
Kelly Anzola ◽  
Filippo Galli ◽  
...  
Keyword(s):  
Decision Making ◽  
Nuclear Medicine ◽  
Treatment Response ◽  
Fungal Infections ◽  
Inflammatory Diseases ◽  
Imaging Techniques ◽  
Nuclear Medicine Imaging ◽  
Tumour Immunology ◽  
Therapy Decision

Background: Molecular nuclear medicine plays a pivotal role for diagnosis in a preclinical phase, in genetically susceptible patients, for radio-guided surgery, for disease relapse evaluation, and for therapy decision-making and follow-up. This is possible thanks to the development of new radiopharmaceuticals to target specific biomarkers of infection, inflammation and tumour immunology. Methods: In this review, we describe the use of specific radiopharmaceuticals for infectious and inflammatory diseases with the aim of fast and accurate diagnosis and treatment follow-up. Furthermore, we focus on specific oncological indications with an emphasis on tumour immunology and visualizing the tumour environment. Results: Molecular nuclear medicine imaging techniques get a foothold in the diagnosis of a variety of infectious and inflammatory diseases, such as bacterial and fungal infections, rheumatoid arthritis, and large vessel vasculitis, but also for treatment response in cancer immunotherapy. Conclusion: Several specific radiopharmaceuticals can be used to improve diagnosis and staging, but also for therapy decision-making and follow-up in infectious, inflammatory and oncological diseases where immune cells are involved. The identification of these cell subpopulations by nuclear medicine techniques would provide personalized medicine for these patients, avoiding side effects and improving therapeutic approaches.

scholarly journals Expression of FOXP3 in Canine Gliomas: Immunohistochemical Study of Tumor-Infiltrating Regulatory Lymphocytes

2019 ◽  
Vol 79 (2) ◽  
pp. 184-193 ◽  
Author(s):  
Dolors Pi Castro ◽  
Roberto José-López ◽  
Francisco Fernández Flores ◽  
Rosa M Rabanal Prados ◽  
Maria Teresa Mandara ◽  
...  
Keyword(s):  
Immune Cell ◽  
Low Grade ◽  
Similar Distribution ◽  
High Grade ◽  
Human Gliomas ◽  
Forkhead Box ◽  
Astrocytic Gliomas ◽  
The Difference ◽  
Regulatory Lymphocytes ◽  
The Brain

Abstract Dogs develop gliomas with similar histopathological features to human gliomas and share with them the limited success of current therapeutic regimens such as surgery and radiation. The tumor microenvironment in gliomas is influenced by immune cell infiltrates. The present study aims to immunohistochemically characterize the tumor-infiltrating lymphocyte (TIL) population of naturally occurring canine gliomas, focusing on the expression of Forkhead box P3-positive (FOXP3+) regulatory T-cells (Tregs). Forty-three canine gliomas were evaluated immunohistochemically for the presence of CD3+, FOXP3+, and CD20+ TILs. In low-grade gliomas, CD3+ TILs were found exclusively within the tumor tissue. In high-grade gliomas, they were present in significantly higher numbers throughout the tumor and in the brain-tumor junction. CD20+ TILs were rarely found in comparison to CD3+ TILs. FOXP3+ TILs shared a similar distribution with CD3+ TILs. The accumulation of FOXP3+ Tregs within the tumor was more pronounced in astrocytic gliomas than in tumors of oligodendroglial lineage and the difference in expression was significant when comparing low-grade oligodendrogliomas and high-grade astrocytomas. Only high-grade astrocytomas presented FOXP3+ cells with tumoral morphology. In spontaneous canine gliomas, TILs display similar characteristics (density and distribution) as described for human gliomas, supporting the use of the dog as an animal model for translational immunotherapeutic studies.

Can the apparent diffusion coefficient differentiate the grade of endometrioid adenocarcinoma and the histological subtype of endometrial cancer?

2017 ◽  
Vol 59 (3) ◽  
pp. 363-370 ◽  
Author(s):  
Bin Yan ◽  
Tingting Zhao ◽  
Xiufen Liang ◽  
Chen Niu ◽  
Caixia Ding
Keyword(s):  
Diffusion Coefficient ◽  
Endometrial Cancer ◽  
Apparent Diffusion Coefficient ◽  
Low Grade ◽  
Endometrioid Adenocarcinoma ◽  
High Grade ◽  
Squamous Differentiation ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Endometrial Cancers

Background Diffusion-weighted imaging (DWI) provides useful information for the identification of benign and malignant uterine lesions. However, the use of the apparent diffusion coefficient (ADC) for histopathological grading of endometrial cancer is controversial. Purpose To explore the use of ADC values in differentiating the preoperative tumor grading of endometrioid adenocarcinomas and investigate the relationship between the ADC values of endometrial cancer and the histological tumor subtype. Material and Methods We retrospectively evaluated 98 patients with endometrial cancers, including both endometrioid adenocarcinomas (n = 80) and non-endometrioid adenocarcinomas (n = 18). All patients underwent DWI procedures and ADC values were calculated. The Kruskal–Wallis test and the independent samples Mann–Whitney U test were used to compare differences in the ADC values between different tumor grades and different histological subtypes. Results The mean ADC values (ADCmean) for high-grade endometrioid adenocarcinomas were significantly lower than the values for low-grade tumors (0.800 versus 0.962 × 10–3 mm2/s) ( P = 0.002). However, no significant differences in ADCmean and minimum ADC values (ADCmin) were found between tumor grades (G1, G2, and G3) of endometrial cancer. Compared with endometrioid adenocarcinomas, the adenocarcinoma with squamous differentiation showed lower ADC values (mean/minimum = 0.863/0.636 versus 0.962/0.689 × 10–3 mm2/s), but the differences were not significant ( Pmean = 0.074, Pmin = 0.441). Moreover, ADCmean for carcinosarcomas was significantly higher than the value for G3 non-carcinosarcoma endometrial cancers (1.047 versus 0.823 × 10–3 mm2/s) ( P = 0.001). Conclusion The ADCmean was useful for identifying high-grade and low-grade endometrioid adenocarcinomas. Additionally, squamous differentiation may decrease ADCmean and ADCmin of endometrioid adenocarcinoma, and carcinosarcomas showed relatively high ADCmean.

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