Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors

Overcast, Wynton B; Davis, Korbin; Ho, Chang Yueh; Hutchins, Gary D.; Green, Mark; Graner, Brian; Veronesi, Michael C.

doi:10.1007/s11912-021-01020-2

Cited by 72 publications

(55 citation statements)

References 154 publications

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“…MRI provides excellent soft tissue contrast and spatial resolution without ionizing radiation, which has been widely used due to its relatively low cost and easy accessibility ( Mirzaei and Adeli, 2018 ). Meanwhile, PET imaging has been widely utilized in the diagnosis and management of cancer patients with relatively high sensitivity and quantitative-imaging ability ( Shankar et al, 2020 ; Overcast et al, 2021 ). However, these imaging examinations have showed a limited ability in the imaging of CNS-L mainly due to the special histopathological characteristics of the disease.…”

Section: Discussionmentioning

confidence: 99%

Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice

Zhang

Chen

et al. 2022

Front. Bioeng. Biotechnol.

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Central nervous system leukemia (CNS-L) is caused by leukemic cells infiltrating into the meninges or brain parenchyma and remains the main reason for disease relapse. Currently, it is hard to detect CNS-L accurately by clinically available imaging models due to the relatively low amount of tumor cells, confined blood supply, and the inferior glucose metabolism intensity. Recently, integrin α6-laminin interactions have been identified to mediate CNS-L, which suggests that integrin α6 may be a promising molecular imaging target for the detection of CNS-L. The acute lymphoblastic leukemia (ALL) cell line NALM6 stabled and transfected with luciferase was used to establish the CNS-L mouse model. CNS-L-bearing mice were monitored and confirmed by bioluminescence imaging. Three of our previously developed integrin α6-targeted peptide-based molecular imaging agents, Cy5-S5 for near-infrared fluorescence (NIRF), Gd-S5 for magnetic resonance (MR), and 18F-S5 for positron emission tomography (PET) imaging, were employed for the molecular imaging of these CNS-L-bearing mice. Bioluminescence imaging showed a local intensive signal in the heads among CNS-L-bearing mice; meanwhile, Cy5-S5/NIRF imaging produced intensive fluorescence intensity in the same head regions. Moreover, Gd-S5/MR imaging generated superior MR signal enhancement at the site of meninges, which were located between the skull bone and brain parenchyma. Comparatively, MR imaging with the clinically available MR enhancer Gd-DTPA did not produce the distinguishable MR signal in the same head regions. Additionally, 18F-S5/PET imaging also generated focal radio-concentration at the same head regions, which generated nearly 5-times tumor-to-background ratio compared to the clinically available PET radiotracer 18F-FDG. Finally, pathological examination identified layer-displayed leukemic cells in the superficial part of the brain parenchyma tissue, and immunohistochemical staining confirmed the overexpression of the integrin α6 within the lesion. These findings suggest the potential application of these integrin α6-targeted molecular imaging agents for the accurate detection of CNS-L.

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Section: Discussionmentioning

confidence: 99%

Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice

Zhang

Chen

et al. 2022

Front. Bioeng. Biotechnol.

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“…Clinical use of amino acid PET tracers for evaluation of metastatic disease in the brain has recently been recommended by an international working group, known as the Response Assessment in Neuro-Oncology (RANO) working group. They contend that amino acid PET imaging should be used in addition to MRI, primarily because MRI alone has limitations when evaluating therapy response, especially after radiation (26)(27)(28)(29). The most thoroughly researched indication for using amino acid PET imaging for brain metastases has been to discriminate between radiation injury and recurrent disease.…”

Section: Amino Acidsmentioning

confidence: 99%

“…In Europe, utilizing amino acid PET has specifically been shown to be cost effective in distinguishing recurrent metastatic tumor from post radiation changes in the brain. 18F-FET in particular has the most evidence supporting its use for this indication (27). A disadvantage to amino acid PET is that studies are scarce with regards to uptake in untreated metastatic disease in the brain (26).…”

Section: Amino Acidsmentioning

confidence: 99%

“…The mechanism of action for these amino acid PET tracers is that uptake is mainly via the L-type amino acid transporters, LAT1 and/or LAT2, which transport large neutral amino acids. There is high expression of these transporters in tumor cells due to a need to rev up protein synthesis (27)(28)(29). Of note, 18F-FACBC also utilizes the alanine, serine, and cysteine transporter 2 (ASCT2), which is also overexpressed in many malignancies.…”

Section: Amino Acidsmentioning

confidence: 99%

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Molecular Imaging of Brain Metastases with PET

Schroeder,

Hall

2022

Metastasis

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Molecular imaging of brain metastases with positron emission tomography with computed tomography (PET/CT) or with magnetic resonance imaging (PET/MRI) can be performed with a growing number of molecular imaging agents. The most commonly used molecular imaging agent for primary malignancies outside of the brain is a glucose analog radio-labelled with fluorine-18, 18F-fluorodeoxyglucose (18F-FDG), which can be used to identify brain metastases. Likewise, additional molecular imaging agents such as prostate specific membrane antigen (PSMA) ligands (i.e., 68Ga-PSMA-11), alkylphosphocholine analogs (i.e., CLR124/CLR1404), and amino acids (i.e., 11C-MET, 18F-FET, 18F-DOPA, 18F-FACBC) can identify brain metastases. Advantages of PET in brain tumor imaging include co-registration with other imaging technologies, quantitative measurements, and significant potential for improvement in diagnostic accuracy. PET can be used to detect brain metastases while imaging for other Note to the Reader: This chapter is part of the book Metastasis (ISBN: 978-0-6453320-2-5), scheduled for publication in April 2022. The book is being published by Exon Publications,

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“…In addition to intraoperative DES, presurgical imaging is paramount to achieve an optimized onco-functional result. At the forefront of imaging techniques, multi-sequence magnetic resonance imaging (MRI) is applied to gather insights into spatial location, spread, and phenotyping of brain tumors (23)(24)(25)(26). Lately, diffusion tensor imaging (DTI) in particular has seen increasing relevance as it allows identifying and delineating subcortical white matter (WM) structures non-invasively (27)(28)(29)(30)(31).…”

Section: Introductionmentioning

confidence: 99%

Tracking the Corticospinal Tract in Patients With High-Grade Glioma: Clinical Evaluation of Multi-Level Fiber Tracking and Comparison to Conventional Deterministic Approaches

et al. 2021

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While the diagnosis of high-grade glioma (HGG) is still associated with a considerably poor prognosis, neurosurgical tumor resection provides an opportunity for prolonged survival and improved quality of life for affected patients. However, successful tumor resection is dependent on a proper surgical planning to avoid surgery-induced functional deficits whilst achieving a maximum extent of resection (EOR). With diffusion magnetic resonance imaging (MRI) providing insight into individual white matter neuroanatomy, the challenge remains to disentangle that information as correctly and as completely as possible. In particular, due to the lack of sensitivity and accuracy, the clinical value of widely used diffusion tensor imaging (DTI)-based tractography is increasingly questioned. We evaluated whether the recently developed multi-level fiber tracking (MLFT) technique can improve tractography of the corticospinal tract (CST) in patients with motor-eloquent HGGs. Forty patients with therapy-naïve HGGs (mean age: 62.6 ± 13.4 years, 57.5% males) and preoperative diffusion MRI [repetition time (TR)/echo time (TE): 5000/78 ms, voxel size: 2x2x2 mm3, one volume at b=0 s/mm2, 32 volumes at b=1000 s/mm2] underwent reconstruction of the CST of the tumor-affected and unaffected hemispheres using MLFT in addition to deterministic DTI-based and deterministic constrained spherical deconvolution (CSD)-based fiber tractography. The brain stem was used as a seeding region, with a motor cortex mask serving as a target region for MLFT and a region of interest (ROI) for the other two algorithms. Application of the MLFT method substantially improved bundle reconstruction, leading to CST bundles with higher radial extent compared to the two other algorithms (delineation of CST fanning with a wider range; median radial extent for tumor-affected vs. unaffected hemisphere – DTI: 19.46° vs. 18.99°, p=0.8931; CSD: 30.54° vs. 27.63°, p=0.0546; MLFT: 81.17° vs. 74.59°, p=0.0134). In addition, reconstructions by MLFT and CSD-based tractography nearly completely included respective bundles derived from DTI-based tractography, which was however favorable for MLFT compared to CSD-based tractography (median coverage of the DTI-based CST for affected vs. unaffected hemispheres – CSD: 68.16% vs. 77.59%, p=0.0075; MLFT: 93.09% vs. 95.49%; p=0.0046). Thus, a more complete picture of the CST in patients with motor-eloquent HGGs might be achieved based on routinely acquired diffusion MRI data using MLFT.

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Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors

Cited by 72 publications

References 154 publications

Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice

Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice

Molecular Imaging of Brain Metastases with PET

Tracking the Corticospinal Tract in Patients With High-Grade Glioma: Clinical Evaluation of Multi-Level Fiber Tracking and Comparison to Conventional Deterministic Approaches

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