Key points
-
Tumors demonstrate substantial inter- and intratumor heterogeneity in their biological features
-
Imaging techniques may improve the assessment of tumor-specific characteristics in clinical practice.
-
Functional and molecular imaging techniques may depict tumor heterogeneity.
Introduction
Imaging for the evaluation of tumor biology
Tumor macrostructural characteristics on imaging
Tumor morphology
Biophysical characteristics of tumors: stiffness and elasticity
Technical features
Biological bases of elastography
Interpretation guidelines
Clinical value
Tumor microstructure and composition on imaging
Diffusion-weighted imaging
Technical features
Biological bases of DWI
Interpretation guidelines
-
Qualitative evaluation
-
Quantitative evaluation
Signal intensity on high b-value images (b800–b1000) | Relative value on apparent diffusion coefficient (ADC) maps | Signal intensity on T2-weighted images | Interpretation |
---|---|---|---|
High | Low | Intermediate | Generally, high cellularity tumor Coagulative necrosis Abscess Rarely high protein content |
High | High | High | T2-shine through (often proteinaceous fluid) |
Low | Low | Low | Fibrous tissue with low water content +/- viable tumor |
Low | High | High | Fluid Liquefactive necrosis Lower cellularity/grade tumor Glandular tissue |
Low | High | High | Vasogenic edema (T2-wash out) |
Low | Low | Variable | Hemorrhagic content (T2-black out) |
Clinical value
Tissular composition and imaging
Tumor microenvironment
Imaging of tumor stroma
Imaging of tumor-infiltrating immune cells
Imaging of oxygenation and hypoxia in cancer
Biological bases of tumor hypoxia
Technical features
-
Oxygen-enhanced MRI
-
Radiotracers
Clinical value
Imaging of tumor pH (acidosis)
Imaging the expression of specific molecular characteristics
Radiotracer | Biological Correlation | Tumor Type | Main indications |
---|---|---|---|
FDG | Energetic glycolytic metabolism | Many tumor types | Diagnosis, staging, response, prognostic value, relapsing tumor |
Choline radiotracers | Cellular membrane turnover and phosphatidylcholine metabolism | Prostate Bladder, Brain | Diagnosis, staging, relapsing tumor |
Methionine | Amino acid transport and protein synthesis | Brain and head and neck | Diagnosis, grading, response, prognostic value, relapsing tumor |
Acetate | Lipid synthesis and energetic metabolism | Prostate Hepatocellular carcinoma | Diagnosis, staging, relapsing tumor |
DOPA | Dopamine uptake and metabolism | Neuroendocrine tumors | Diagnosis, staging, relapsing tumor |
FLT | Cellular proliferation and tyrosine kinases-1 activity | Lung, Lymphoma, Colorectal. Gastric and Pancreas | Diagnosis and tumor response |
Sigma-2 (σ2) Receptor | σ2 receptors are expressed in proliferating tumor cells | Diagnosis and treatment evaluation | |
Integrin targeted Imaging agents (RGD) and VEGFR targeted Imaging agents | Angiogenesis | Preclinical use | |
Annexin V | Tumor Apoptosis | Preclinical use | |
Nitroimidazoles (FAZA, FMISO) Cu-ATSM | Tumor hypoxia | Preclinical use | |
Radiotracers Specific Tumor Types | |||
Radiotracers Targeting Specific Tumor Markers | EGFR expression PSMA expression Chemokine receptor type 4 (CXCR4) DOTA-peptides (Somatostatin receptors) Bombesin receptors | Lung, Colorectal Prostate Breast and head and neck cancer metastasis Neuroendocrine tumors Prostate, breast, small cell lung cancer, GIST | Preclinical use Relapsing tumor. Staging and tumor response Preclinical use Diagnosis, staging, relapsing tumor, response assessment |
Non-Tumoral metabolic pathways | |||
NaF | Bone metabolism (non-specific tumor tracer) | Bone metastases | Diagnosis and staging |
Clinical value
Imaging main tumor hallmarks
Tumor metabolic reprogramming
Molecular imaging with radiotracers
-
Energetic metabolism (glycolysis)
-
Biosynthetic metabolism
Technical features
Interpretation guidelines
Clinical value
-
FDG-PET imaging
-
Non-FDG PET imaging
MR spectroscopy
Molecular and biochemical bases of cancer evaluation with MRS/MRSI
Metabolite | Biological meaning | ppm | Decreased values | Increased values |
---|---|---|---|---|
Cho (total Cho-containing compounds) | A metabolic marker cell membrane synthesis and repair. Related to cell density and membrane integrity | 3.22 | Due to cell proliferation and to breakdown of cell membranes. Higher Cho levels are shown in higher grade tumors compared with lower-grade tumors | |
Cr (from both creatine and phosphocreatine, often called referred to as total creatine peak) | Reflects “cellular energetics” | 3.02 | Decreased phospocreatine (PCr) is an inconstant finding in tumors. Represents a low- energy status of glycolisis in primary tumors (high grade gliomas) and in metastatic tumors is the effect of the lack of PCr in most tissues. | |
Lac | Glycolysis Usually lactate is present only in minimun amounts (i.e., in the brain) and is not depicted using the normal spectroscopic techniques. | Doublet peak at 1.33 ppm | Increased Lac is the effect of the high rate of glycolisis. Lac is an end product of glycolysis and increases rapidly during hypoxia It accumulates in necrotic or cystic areas | |
Lip | May indicated tumor necrosis or voxel contamination by diploic space fat, scalp and subcutaneous tissue | 0.9 and 1.3ppm | The rise of Lip is detected in various cellular processes such as necrosis, growth arrest, inflammation, malignancy and apoptosis. | |
Specific metabolites in brain H-MRS | ||||
NAA | A marker of neuronal and axonal density and viability The exact role of NAA in human brain metabolism is uncertain. It is postulated to be involved in lipogenesis pathways Largest peak in a “normal” H- MRS brain spectrum. | 2.02 | Absence of neurons and axons in most tumors but also in white matter diseases (i.e., multiple sclerosis) | |
mI | A glial marker located in astrocytes Involved in osmoregulation and volume regulation | 3.56 | It is a relative marker for low-grade gliomas. Reduced in high-grade tumors | |
Specific metabolites in Prostate H-MRS | ||||
Ci | Normal human prostate gland accumulates and secretes extraordinarily high Ci levels | 2.6 | In prostate cancer Ci levels fall due to consumption of Ci to supply energy to proliferating cells) |
Technical features
Interpretation guidelines
Clinical value
-
Hydrogen MRS
-
Phosphorus MRS
-
Hyperpolarized MRSI
Imaging tumor proliferation
Biological bases of tumor proliferation
Imaging approaches to tumor proliferation
-
PET imaging of tumor proliferation
Evaluation of tumor vasculature-angiogenesis
Biological bases of angiogenesis
Technical features
Interpretation guidelines
-
Qualitative analysis: Visual assessment of pre- and postcontrast images, or of the shape of the time-intensity curves (TIC) represents the most simple way of analysis. Curve characteristics, including the speed of the filling phase, the maximum peak intensity, and the morphology following the peak of enhancement (persistent increase, plateau, or washout), are evaluated. This approach has shown clinical utility for the characterization of breast, soft-tissue, and prostate tumors, although does not produce a quantifiable index.
-
Semiquantitative analysis: This type of evaluation is based on performing a direct analysis of changes in SI using semiquantitative indices. Main descriptors that characterize the shape and structure of the curves include time to peak enhancement, initial area under the curve (IAUC), maximum enhancement, etc. These parameters have been used in the clinical evaluation of brain, breast, and prostate tumors. Unfortunately, they do not present a clear defined relationship with tumor physiology.
-
Quantitative analysis: The combination of DCE imaging with mathematical modeling of the contrast agent kinetics enables quantitative assessment of the structural and functional changes in tumor microvasculature. Measured TICs must be converted into concentration of contrast–time curves and modeled in a pixel-wise fashion to create functional maps of vascular parameters. In general, the complexity of the quantitative analysis and the lack of consensus have limited its applications to clinical trials in academic centers.