A reference-based approach using whole-brain segmentation for image-derived PET input functions in CBF, OEF, and...

Area of Science:

• Neuroimaging
• Nuclear Medicine
• Cerebrovascular Physiology

Background:

• Quantitative measurements of cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO₂) using ¹⁵O-labeled PET typically require invasive arterial input function (AIF) measurements.
• Arterial blood sampling poses risks and logistical challenges in clinical settings.

Purpose of the Study:

• To develop and validate a fully noninvasive method for reconstructing an image-derived input function (IDIF) directly from dynamic ¹⁵O₂-H₂¹⁵O PET data.
• To enable accurate, noninvasive quantification of CBF, OEF, and CMRO₂.

Main Methods:

• A reference-based approach was used with data from 186 subjects with suspected cerebrovascular disease.
• Segment-based reference values from 60 subjects were applied to reconstruct IDIFs in 126 subjects.
• IDIFs were reconstructed using coefficient-of-variation weighted averaging of segmental tissue time-activity curves.

Main Results:

• Estimated IDIFs demonstrated strong agreement with measured AIFs.
• High correlations (r=0.88, p<0.001) and minimal bias (≤0.005) were observed for CBF, OEF, and CMRO₂.
• No significant differences were found between IDIF- and AIF-based quantitative values, although mild regression-to-the-mean was noted in IDIFs.

Conclusions:

• The proposed method reliably estimates input functions from tissue curves without the need for blood sampling.
• This enables fully noninvasive quantification of CBF, OEF, and CMRO₂ using ¹⁵O PET.
• The method is clinically feasible for standard ¹⁵O PET studies but not for quantitative parameter estimation under stimulation.