Late-scan tissue-to-plasma ratio

Simplified PET study protocols are preferred in clinical studies, avoiding arterial cannulation and reducing the scan time. SUV method has several drawbacks, which can be partially solved by using tissue-to-plasma, tissue-to-blood, or tissue-to-reference tissue ratio. These ratios are often called SUV ratios (SUVR, SUR), but the units cancel out in ratio calculation, and activity concentrations can be used directly to calculate the ratios. Tissue-to-blood ratio is particularly attractive method for diagnostic studies, if it is possible to extract blood activity from the image.

Reversible uptake

When tracer uptake is reversible, tissue-to-plasma ratios stabilize sooner or later, and the ratio will be correlated (linearly or non-linearly) with the equilibrium volume of distribution (VT) of the tracer in the tissue.

Lehtiö et al (2003) showed with hypoxia tracer [18F]FETNIM in tumours that simple tissue-to-plasma ratio correlated well with VT - more accurate quantification of VT would require dynamic imaging and arterial blood sampling (or image-derived input). In contrast, tumour-to-muscle ratio which is commonly used in oncology did not show any correlation with VT (Lehtiö et al., 2003).

Mitkovski et al (2005) have validated the use of “simplified distribution volume” from a single 90-120 min PET scan for 2[18F]F-A-85380.

Irreversible uptake

When tracer uptake is irreversible during the PET scan, tissue-to-plasma ratio at a late time point correlates with the net tissue uptake of the tracer. This has been proved both theoretically and in practice in tumour [18F]FDG studies (van den Hoff et al., 2013), and in the brain and liver (Keramida & Peters, 2019). Tumour-to-blood ratio provides better prognostic factors than tumour-to-liver ratio, while SUV is the weakest method (Hofheinz et al., 2016).

In case of [18F]FDG the plasma TAC can be substituted with blood TAC.

Calculation of tissue-to-plasma ratio image

Before calculation, one must be sure that PET image is corrected for physical decay to the time of tracer administration, like the plasma (or blood) data is.

From a single-scan (static) PET study, the ratio image can be calculated using imgcalc, with the plasma radioactivity concentration during the PET scan as the divider. If the plasma (or blood) concentration is derived from a blood pool in the image, then the decay correction or calibration is of no concern.

For validation of the tissue-to-plasma method, the results should be compared to proper quantitative methods which require dynamic studies. Dynamic tissue-to-plasma ratio image may have to be calculated from a dynamic PET study and metabolite corrected plasma curve to study the time-course of the ratio. This can be accomplished by using imgratio. For validation, the regional tissue-to-plasma ratios may have to be calculated from a dynamic PET study and metabolite corrected plasma curve. This can be accomplished by using dftratio. To simulate single-scan PET study, the “static” image can be made from dynamic image with imginteg with option -avg.

Ratio images can be processed further as any parametric images, and regional ratios can be calculated for instance with Carimas.

Calculation of regional tissue-to-plasma ratios

Before calculation, one must be sure that tissue data is corrected for physical decay to the time of tracer administration.

From the regional radioactivity concentration values (TAC files) of a single-scan (static) PET study, the regional tissue-to-plasma ratios can be easily calculated using a spreadsheet software or using taccalc, with the (metabolite corrected) plasma radioactivity concentration during the PET scan as the divider. If taccalc is used, then the ratios are saved in TAC format, and can be viewed for example in web browser or Excel after conversion to HTML or XML table or CSV format, or converted into result file format for further processing.

The regional tissue-to-plasma ratios between a certain time range can be calculated using dftratio.

References:

van den Hoff J, Oehme L, Schramm G, Maus J, Lougovski A, Petr J, Beuthien-Baumann B, Hofheinz F. The PET-derived tumor-to-blood standard uptake ratio (SUR) is superior to tumor SUV as a surrogate parameter of the metabolic rate of FDG. EJNMMI Res. 2013; 3: 77. doi: 10.1186/2191-219X-3-77.

Lehtiö K, Oikonen V, Nyman S, Grönroos T, Roivainen A, Eskola O, Minn H. Quantifying tumour hypoxia with fluorine-18 fluoroerythronitroimidazole ([18F]FETNIM) and PET using the tumour to plasma ratio. Eur J Nucl Med Mol Imaging 2003; 30(1): 101-108. doi: 10.1007/s00259-002-1016-x.

Mitkovski S, Villemagne VL, Novakovic KE, O’Keefe G, Tochon-Danguy H, Mulligan RS, Dickinson KL, Saunder T, Gregoire MC, Bottlaender M, Dolle F, Rowe CC. Simplified quantification of nicotinic receptors with 2[18F]F-A-85380 PET. Nucl Med Biol. 2005; 32(6): 585-591. doi: 10.1016/j.nucmedbio.2005.04.013.

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Updated at: 2019-11-26
Created at: 2007-11-23
Written by: Vesa Oikonen