Quantitative multimodality imaging in cancer research and therapy

Yankeelov, Thomas E.; Abramson, Richard G.; Quarles, C. Chad

doi:10.1038/nrclinonc.2014.134

Cited by 108 publications

(90 citation statements)

References 71 publications

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“…As of today, SUV remains a standard metric for PETbased diagnosis and therapy response assessment in oncology [68,69]. However, the SUV represents only a simplified measure to describe a physiological process.…”

Section: Quantification In Pet and Spectmentioning

confidence: 99%

Hybrid Imaging: Instrumentation and Data Processing

et al. 2018

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State-of-the-art patient management frequently requires the use of non-invasive imaging methods to assess the anatomy, function or molecular-biological conditions of patients or study subjects. Such imaging methods can be singular, providing either anatomical or molecular information, or they can be combined, thus, providing "anato-metabolic" information. Hybrid imaging denotes image acquisitions on systems that physically combine complementary imaging modalities for an improved diagnostic accuracy and confidence as well as for increased patient comfort. The physical combination of formerly independent imaging modalities was driven by leading innovators in the field of clinical research and benefited from technological advances that permitted the operation of PET and MR in close physical proximity, for example. This review covers milestones of the development of various hybrid imaging systems for use in clinical practice and small-animal research. Special attention is given to technological advances that helped the adoption of hybrid imaging, as well as to introducing methodological concepts that benefit from the availability of complementary anatomical and biological information, such as new types of image reconstruction and data correction schemes. The ultimate goal of hybrid imaging is to provide useful, complementary and quantitative information during patient work-up. Hybrid imaging also opens the door to multi-parametric assessment of diseases, which will help us better understand the causes of various diseases that currently contribute to a large fraction of healthcare costs.

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Section: Quantification In Pet and Spectmentioning

confidence: 99%

Hybrid Imaging: Instrumentation and Data Processing

et al. 2018

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“…For example, lesions 1 and 2 ( Fig. 4A) have similar k 3 (0.0068 min 21 and 0.0074 min 21 , respectively), but their TBRs are markedly different due to different DVs (TBR 5 2.49; DV 5 1.24 and TBR 5 1.08; DV 5 0.59, respectively). Consider also lesion 3, which has a TBR (1.08) identical to lesion 2 but has a DV of 1.09 and is normoxic (k 3 5 0.0000 min 21 ).…”

Section: Population-based Comparison Of K 3 and Tbrmentioning

confidence: 99%

“…The analogous scatterplot for the pooled voxelwise data is presented in Figure 4B (r 5 0.74), with superimposed nominal hypoxia thresholds based on a TBR of 1.4 and the regressionequivalent k 3 of 0.0031 min 21 . These thresholds split the plane into 4 quadrants where the first and third quadrants contain voxels that would be classified identically by both TBR and k 3 criteria; the second and fourth quadrants contain voxels where the criteria disagree.…”

Section: Population-based Comparison Of K 3 and Tbrmentioning

confidence: 99%

“…A complex relationship between tumor hypoxia, perfusion, and glucose metabolism supports the use of composite metrics that offer additional information on tumor adaptation to the microenvironment (17,18) and may be better predictors of overall survival (19,20). However, protocols incorporating several PET radiotracers administered in multiple imaging sessions can become overly complex and may be restricted by regulatory limits on ionizing radiation exposure (21). Moreover, despite reports that pharmacokinetic model-based metrics derived from 18 F-FMISO or 18 F-FDG dynamic PET (dPET) studies confer advantage over static uptake-based indices (19,(22)(23)(24), dPET protocols have not yet been widely adopted, in part due to their clinical impracticality.…”

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Multiparametric Imaging of Tumor Hypoxia and Perfusion with¹⁸F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer

et al. 2017

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Tumor hypoxia and perfusion are independent prognostic indicators of patient outcome. We developed the methodology for and investigated the utility of multiparametric imaging of tumor hypoxia and perfusion with 18 F-fluoromisonidazole ( 18 F-FMISO) dynamic PET (dPET) in head and neck cancer. Methods: One hundred twenty head and neck cancer patients underwent 0-to 30-min 18 F-FMISO dPET in a customized immobilization mask, followed by 10-min static acquisitions starting at 93 6 6 and 160 6 13 min after injection. A total of 248 lesions ($2 cm 3 ) were analyzed. Voxelwise pharmacokinetic modeling was conducted using an irreversible 1-plasma 2-tissuecompartment model to calculate surrogate biomarkers of tumor hypoxia (k 3 ), perfusion (K 1 ), and 18 F-FMISO distribution volume. The analysis was repeated with truncated dPET datasets. Results: Substantial inter-and intratumor heterogeneity was observed for all investigated metrics. Equilibration between the blood and unbound 18 F-FMISO was rapid in all tumors. 18 F-FMISO distribution volume deviated from the expected value of unity, causing discrepancy between k 3 maps and total 18 F-FMISO uptake and reducing the dynamic range of total 18 F-FMISO uptake for quantifying the degree of hypoxia. Both positive and negative trends between hypoxia and perfusion were observed in individual lesions. All investigated metrics were reproducible when calculated from a truncated 20-min dataset. Conclusion: 18 F-FMISO dPET provides the data necessary to generate parametric maps of tumor hypoxia, perfusion, and radiotracer distribution volume. These data clarify the ambiguity in interpreting 18 F-FMISO uptake and improve the characterization of lesions. We show total acquisition times can be reduced to 20 min, facilitating the translation of 18 F-FMISO dPET into the clinic.

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“…MRI is a widely used clinical imaging modality that provides exquisite soft-tissue contrast without using ionizing radiation (6,7). More than 35% of MRI scans use MRI contrast agents, particularly paramagnetic gadolinium (Gd 3+ )-based contrast agents, which shorten T 1 and lead to an increase in MRI intensity (8).…”

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confidence: 99%

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

Xue

Yang²,

Qiao

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

119

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With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd 3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd 3+ and a 10 11 -fold greater selectivity for Gd 3+ over Zn 2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r 1 /r 2 : 66.8 mmol −1 ·s −1 / 89.2 mmol −1 ·s −1 per particle). Using T 1 -and T 2 -weighted, as well as T 2 /T 1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.MRI | uveal melanoma | metastasis | contrast agents | T 2 /T 1 ratio imaging T umor metastasis is the main cause of nearly all human cancerrelated deaths. Liver is a common site for metastases of a variety of cancers, including melanoma, breast, pancreatic, and colon cancers (1, 2). For example, uveal melanoma, the most common primary intraocular tumor, has a 40% risk of metastasizing to the liver within 10 y of diagnosis of the primary tumor. Hepatic metastases, which occur in 95% of patients with uveal melanoma metastasis, result in death in almost all cases. This high death rate is related to the recognition of liver metastasis at a late clinical stage (at stage II or later in the TNM system) in which the metastatic uveal melanoma is resistant to currently available systemic chemotherapies (3, 4). The liver may also give rise to primary tumors such as hepatocellular carcinoma (HCC), which is the most common primary malignancy worldwide (5). However, currently there is no reliable way to detect primary liver cancer and hepatic metastases at early stages with high sensitivity and specificity.MRI is a widely used clinical imaging modality that provides exquisite soft-tissue contrast without using ionizing radiation (6, 7). More than 35% of MRI scans use MRI contrast agents, particularly paramagnetic gadolinium (Gd 3+ )-based contrast agents, which shorten T 1 and lead to an increase in MRI intensity (8). All clinically approved Gd 3+ -containing contrast agents are based on small chelators with relaxivity (r 1 and r 2 ) values around 4-6 mM −1 ·s −1 . Their low relaxivities severely limit the sensitivity of current MR imaging methods with respect to detection of lesions and treatment planning and monitoring. Repeat MRI scans are frequently requested for patients with ambiguous small lesions and are used as a routine follow-up modality for highrisk patients, but t...

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Quantitative multimodality imaging in cancer research and therapy

Cited by 108 publications

References 71 publications

Hybrid Imaging: Instrumentation and Data Processing

Hybrid Imaging: Instrumentation and Data Processing

Multiparametric Imaging of Tumor Hypoxia and Perfusion with¹⁸F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

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Quantitative multimodality imaging in cancer research and therapy

Cited by 108 publications

References 71 publications

Hybrid Imaging: Instrumentation and Data Processing

Hybrid Imaging: Instrumentation and Data Processing

Multiparametric Imaging of Tumor Hypoxia and Perfusion with18F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer

Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

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Multiparametric Imaging of Tumor Hypoxia and Perfusion with¹⁸F-Fluoromisonidazole Dynamic PET in Head and Neck Cancer