What is functional imaging in medical imaging?

Functional Imaging in Medical Imaging

Functional imaging refers to imaging techniques that visualize how tissues and organs function physiologically, rather than just their anatomical structure, by detecting metabolic activity, perfusion, blood flow, or physiological responses to stress. 1

Core Concept and Distinction from Anatomical Imaging

Functional imaging provides information about tissue physiology and metabolic processes, contrasting with anatomical imaging (CT, standard MRI) that primarily shows structural details. 2, 3 This distinction is particularly important because:

• Functional changes often precede structural changes in disease processes, allowing earlier detection of pathology 4
• Structural imaging may appear normal while functional imaging reveals significant abnormalities, particularly in epilepsy where up to 58% of patients with surgically proven focal cortical dysplasia had normal MRI 1
• Functional imaging can identify physiologically significant lesions when multiple structural abnormalities are present, helping determine which are clinically relevant 1

Primary Functional Imaging Modalities

Nuclear Medicine Techniques

• PET (Positron Emission Tomography): Measures metabolic activity, particularly glucose metabolism with FDG-PET, showing sensitivity of 63-67% for localizing epileptogenic lesions and specificity of 94% in nonlesional epilepsy 1
• SPECT (Single Photon Emission Computed Tomography): Assesses regional cerebral blood flow and perfusion patterns using tracers like Tc-99m HMPAO or Tc-99m-ECD 1, 4

MRI-Based Functional Techniques

• Stress perfusion imaging: Detects myocardial ischemia by identifying perfusion defects during exercise or pharmacological stress, with superior diagnostic performance compared to exercise ECG 1
• Stress wall motion imaging: Identifies stress-induced wall motion abnormalities indicating ischemia 1
• fMRI (functional MRI): Uses BOLD (blood oxygen level-dependent) technique to detect changes in brain activity by measuring hemodynamic responses 1, 3
• MR spectroscopy: Measures metabolic compounds like N-acetylaspartate, creatine, choline, and lactate to assess neuronal integrity and cellular metabolism 1

Clinical Applications by Organ System

Cardiac Imaging

Functional imaging is the preferred diagnostic approach for detecting flow-limiting coronary stenosis, with accuracy superior to anatomical imaging alone. 1 Key applications include:

• Ischemia detection: Stress-induced perfusion defects or wall motion abnormalities corresponding to ≥10% of left ventricular myocardium indicate moderate-severe ischemia associated with annual cardiovascular death or MI rate >3% 1
• Prognostic stratification: Normal functional tests predict excellent prognosis with <1% annual rate of cardiac death or MI 1
• Viability assessment: Multiple techniques (PET, SPECT, dobutamine stress echo) assess myocardial viability to guide revascularization decisions in chronic ischemic LV dysfunction 1

Neurological Imaging

Functional imaging is most utilized when surgical intervention is contemplated or when structural MRI is normal or shows nonspecific findings. 1 Applications include:

• Epilepsy evaluation: FDG-PET shows statistically significantly better detection power than MRI (P=0.013) for epileptogenic foci, with approximately 31% of drug-resistant epilepsy patients selected for surgery based on PET results 1
• Seizure focus localization: SPECT or SPECT/CT can identify seizure foci that are occult on anatomical imaging 1
• Traumatic brain injury: Despite promising research findings, there is insufficient evidence to support routine clinical use of SPECT or fMRI at the individual patient level for head trauma 1

Musculoskeletal Imaging

Functional MRI techniques address bone marrow, muscle, and nerve function using spectroscopy, perfusion imaging, BOLD imaging, and diffusion tensor imaging (DTI). 2 These techniques help bridge the disconnect between structural appearances and clinical symptoms. 2

Key Advantages Over Anatomical Imaging

• Higher sensitivity for functionally significant disease: Functional tests using invasive FFR as reference standard show high accuracy for detecting flow-limiting stenosis 1
• Localization capability: Functional imaging indicates the location and extent of ischemia or dysfunction, not just presence of disease 1
• Prognostic value: Extent of functional abnormality (e.g., >10% ischemic myocardium) provides risk stratification independent of anatomical findings 1
• Fewer unnecessary invasive procedures: Functional imaging strategies result in fewer referrals for downstream invasive angiography compared to anatomical imaging strategies 1

Important Clinical Caveats

A normal functional test does not exclude underlying structural disease—lower grade atherosclerosis not causing ischemia remains undetected by functional testing. 1 Patients with negative functional tests still require risk factor modification based on standard recommendations. 1

Functional imaging has limitations in spatial resolution compared to anatomical imaging, and interpretation requires expertise in recognizing artifacts and technical limitations. 1 The high dimensionality of functional imaging data and flexibility in analysis can contribute to false-positive findings if not properly controlled. 1

Combined anatomical and functional imaging (hybrid imaging) may provide complementary information, with spatial correlation of structural and functional findings facilitating comprehensive interpretation, though large multicenter validation studies are lacking. 1