From anatomy to cellular processes
Historically, diagnostic radiology relied exclusively on morphological information. Basic tissue contrast was formed due to the difference in X-ray attenuation during computed tomography or due to different water content in tissues during magnetic resonance imaging. The main task was simply to detect a mass lesion and differentiate it from healthy tissue.
Today, this approach is being replaced by an in-depth study of fundamental molecular, cellular, and tissue changes. These data form the basis for creating imaging biomarkers (imaging biomarkers). New biomarkers significantly outperform traditional methods in sensitivity and specificity, as they capture not just an anatomical defect, but a pathological process. For example, special CT and MRI modes with contrast agents allow targeted evaluation of tumor angiogenesis, while positron emission tomography using radiopharmaceuticals (PET tracers) reveals shifts in cell proliferation and energy metabolism.
Therapy assessment and companion biomarkers
Traditionally, the efficacy of radiation therapy and chemotherapy was evaluated by changes in the physical dimensions of the tumor node. For this purpose, RECIST (Response Evaluation Criteria In Solid Tumours) criteria were used. However, with the advent of modern drugs, this algorithm required revision.
The introduction of drugs targeting specific molecular targets (e.g., sunitinib or bevacizumab) showed that clinical improvement often occurs without a reduction in tumor diameter. An antivascular drug can provoke massive necrosis of a malignant node, but its initial boundaries on classical scans will remain the same.
Therefore, modifying evaluation criteria is becoming the current standard: morphology is supplemented with functional and metabolic data. The concept of a companion biomarker (companion biomarker) is developing. This is an approach where a targeted drug is prescribed in conjunction with a special diagnostic test. The test visualizes precisely those cellular pathways targeted by the drug, which allows for personalized treatment and moving away from the outdated "one-size-fits-all" paradigm.
Dynamic contrast-enhanced CT
The concepts of molecular and functional imaging partially overlap and are often used together as an alternative to purely morphological methods. A striking example of studying tumor physiology is dynamic contrast-enhanced computed tomography (DCE-CT), also referred to as perfusion CT (perfusion CT).
Although the first attempts to use the method date back to the 1970s, it was the technological leap that made it possible to collect data with high temporal sampling (high temporal sampling) across large volumes of tissue. The method is being actively introduced into clinical practice for a detailed assessment of the vasculature (vasculature), monitoring of antitumor therapy, and management of patients with acute vascular events (strokes).
Case study: glioblastoma multiforme
To understand the diagnostic value of the method, let us consider a case of glioblastoma multiforme (Glioblastoma multiforme). Dynamic contrast-enhanced CT uses a series of sequential scans to calculate microcirculation parameters and construct color parametric maps of the brain.
The physician analyzes several images at once:
- Standard contrast-enhanced CT (Contrast-enhanced CT) provides a basic anatomical picture.
- Regional blood flow map (Regional blood flow) shows the volumetric blood flow rate in the studied area.
- Blood volume map (Blood volume) demonstrates the blood volume fraction in the tissue.
- Permeability surface area product map (Permeability surface area product) visualizes the degree of capillary wall permeability.
When interpreting such maps in a patient with glioblastoma, a vascularized solid component is clearly defined. The permeability map has the highest diagnostic value in this case — it is on this map that the pathological disruption of the blood-brain barrier, characteristic of this malignant tumor, is detected most contrastingly and accurately.
Briefly: answers to topical questions
What specific radiopharmaceuticals are used in PET to assess energy metabolism and tumor cell proliferation?
To assess energy metabolism and tumor cell proliferation during PET, specific radiopharmaceuticals are used that are biomedical analogues of glucose and thymidine.
- 18F-FDG (fluorodeoxyglucose / FDG) is a glucose analogue most commonly used in clinical practice to evaluate glucose metabolism.
- FLT (18F-fluorothymidine / 18F-labelled 3-deoxy-3-fluorothymidine) is a thymidine analogue used to assess cell proliferation and growth.
What modern modifications of RECIST criteria exist for evaluating response to immunotherapy (iRECIST)?
To evaluate the response of solid tumors to immunotherapy, the iRECIST system is used, based on changes in the size of target lesions.
- Complete response (iCR — Complete Response): disappearance of all target lesions.
- Partial response (iPR — Partial Response): decrease in the sum of longest diameters of target lesions by ≥30%.
- Progressive disease (iPD — Progressive Disease): increase in the sum of longest diameters by ≥20% with an absolute increase of ≥5 mm.
- Stable disease (iSD — Stable Disease): condition that does not qualify for response or progression criteria.
The appearance of new lesions is not automatically a sign of progression.
What groups of contrast agents are used for dynamic contrast-enhanced CT?
For dynamic contrast-enhanced CT, low-molecular-weight contrast agents with a mass of less than 1 kDa are used, usually derivatives of iodobenzoic acid. They practically do not bind to serum proteins, and their distribution is similar to that of extracellular fluid. Low-osmolar iodinated contrast agents and iso-osmolar iodixanol are also described in sources; low-osmolar agents are indicated as the standard for diagnostic angiography, and iodixanol as less nephrotoxic compared to some non-ionic low-osmolar agents.
To remember the difference between diagnostic approaches, use the phrase: "Anatomy shows WHERE, function shows HOW, and the molecule shows WHY." Morphological imaging will find the mass, functional imaging will show blood flow features, and molecular imaging will visualize deep cellular pathways.
Class and exam questions
What is an imaging biomarker in oncology?
This is a measurable parameter on a radiological scan that reflects fundamental cellular or tissue changes (e.g., angiogenesis). It allows detecting pathology more accurately than evaluating morphological features alone.
Why have RECIST criteria become insufficient for therapy assessment?
Targeted antivascular drugs can cause total tumor necrosis, but its overall diameter does not change. Classical RECIST criteria, based on size, are unable to reflect such functional improvement.
What is the purpose of a permeability map in brain perfusion CT?
It shows the degree of capillary wall permeability. In brain tumors such as glioblastoma, this map most clearly visualizes the disruption of the blood-brain barrier.
What else to study on this topic
- Magnetic resonance imaging in functional diagnostics
- Positron emission tomography (PET) and metabolism assessment
- Radiopharmaceuticals and novel molecular imaging techniques
- Theranostics: combining diagnostics and targeted therapy
Master the entire topic in the "Diagnostic Radiology" course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Functional and molecular imaging in oncology" and 2,199 more pages of the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 10 video lessons on the subject
Other topics in the "Diagnostic Radiology in Oncology" section
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.