scholarly journals Source-to-Target Automatic Rotating Estimation (STARE) — A publicly-available, blood-free quantification approach for PET tracers with irreversible kinetics: Theoretical framework and validation for [18F]FDG

2021 ◽  
Author(s):  
Elizabeth A Bartlett ◽  
R Todd Ogden ◽  
J John Mann ◽  
Francesca Zanderigo

Introduction: Full quantification of positron emission tomography (PET) data requires an input function. This generally means arterial blood sampling, which is invasive, labor-intensive and burdensome. There is no current, standardized method to fully quantify PET radiotracers with irreversible kinetics in the absence of blood data. Here, we present Source-to-Target Automatic Rotating Estimation (STARE), a novel, data-driven approach to quantify the net influx rate (Ki) of irreversible PET radiotracers, that requires only individual-level PET data and no blood data. We validate STARE with [18F]FDG PET and assess its performance using simulations. Methods: STARE builds upon a source-to-target tissue model, where the tracer time activity curves (TACs) in multiple "target" regions are expressed at once as a function of a "source" region, based on the two-tissue irreversible compartment model, and separates target region Ki from source Ki by fitting the source-to-target model across all target regions simultaneously. To ensure identifiability, data-driven, subject-specific anchoring is used in the STARE minimization, which takes advantage of the PET signal in a vasculature cluster in the FOV that is automatically extracted and partial volume-corrected. To avoid the need for any a priori determination of a single source region, each of the considered regions acts in turn as the source, and a final Ki is estimated in each region by averaging the estimates obtained in each source rotation. Results: In a large dataset of [18F]FDG human scans (N=69), STARE Ki estimates were in good agreement with corresponding arterial blood-based estimates (regression slope=0.88, r=0.80), and were precisely estimated, as assessed by comparing STARE Ki estimates across several runs of the algorithm (coefficient of variation across runs=6.74 ± 2.48%). In simulations, STARE Ki estimates were largely robust to factors that influence the individualized anchoring used within its algorithm. Conclusion: Through simulations and application to [18F]FDG PET data, feasibility is demonstrated for STARE blood-free, data-driven quantification of Ki. Future work will include applying STARE to PET data obtained with a portable PET camera and to other irreversible radiotracers.

1993 ◽  
Vol 11 (11) ◽  
pp. 2101-2111 ◽  
Author(s):  
R L Wahl ◽  
K Zasadny ◽  
M Helvie ◽  
G D Hutchins ◽  
B Weber ◽  
...  

PURPOSE We assessed the feasibility of noninvasive metabolic monitoring of cancer chemohormonotherapy using sequential quantitative positron emission tomographic (PET) scans of tumor glucose metabolism with the glucose analog 2-[18F]-fluoro-2-deoxy-D-glucose (FDG). PATIENTS AND METHODS Eleven women with newly diagnosed primary breast cancers larger than 3 cm in diameter beginning a chemohormonotherapy program underwent a baseline and four follow-up quantitative PET scans during the first three cycles of treatment (days 0 to 63). Tumor response was sequentially determined clinically, radiographically, and then pathologically after nine treatment cycles. RESULTS Eight patients had partial or complete pathologic responses. Their maximal tumor uptake of FDG assessed by PET decreased promptly with treatment to the following: day 8, 78 +/- 9.2% (P < .03); day 21, 68.1 +/- 7.5% (P < .025); day 42, 60 +/- 5.1% (P < .001); day 63, 52.4 +/- 4.4% (P < .0001) of the basal values. Tumor diameter did not decrease significantly during this period through 63 days. Prompt decreases in the FDG influx rate (K) from basal levels (from .019 to .014 mL/cm3/min) after 8 days of treatment (P < .02) and in the estimated rate of FDG phosphorylation to FDG-6-phosphate (k3) from .055 to .038 min-1 after 8 days of treatment (P < .02) to .029 +/- .004 min-1 at 21 days) (P < .02) were observed. Three nonresponding patients had no significant decrease in tumor uptake of FDG (81 +/- 18% of basal value), influx rate (.015 to .012 mL/cm3/min), or tumor size (81 +/- 12% of basal diameter) comparing basal versus 63-day posttreatment values. CONCLUSION Quantitative FDG PET scans of primary breast cancers showed a rapid and significant decrease in tumor glucose metabolism after effective treatment was initiated, with the reduction in metabolism antedating any decrement in tumor size. No significant decrease in FDG uptake (SUV) after three cycles of treatment was observed in the nonresponding patients. FDG PET scanning has substantial promise as an early noninvasive metabolic marker of the efficacy of cancer treatment.


1988 ◽  
Vol 2 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Michio Senda ◽  
Sadahiko Nishizawa ◽  
Yoshiharu Yonekura ◽  
Takao Mukai ◽  
Hideo Saji ◽  
...  

2020 ◽  
pp. 0271678X2092814 ◽  
Author(s):  
Ayla Mansur ◽  
Eugenii A Rabiner ◽  
Hideo Tsukada ◽  
Robert A Comley ◽  
Yvonne Lewis ◽  
...  

Mitochondrial complex I (MC-I) is an essential regulator of brain bioenergetics and can be quantified in the brain using PET radioligand 18F-BCPP-EF. Here we evaluate the test–retest reproducibility of 18F-BCPP-EF in humans, and assess the use of a non-invasive quantification method (standardised uptake value ratio – SUVR). Thirty healthy volunteers had a 90-min dynamic 18F-BCPP-EF scan with arterial blood sampling, five of which received a second scan to be included in the test–retest analysis. Time-activity curves (TAC) were analysed using multilinear analysis 1 (MA1) and the two-tissue compartment model (2TC) to estimate volumes of distribution (VT). Regional SUVR-1 values were calculated from the 70 to 90-min TAC data using the centrum semiovale as a pseudo reference region, and compared to kinetic analysis-derived outcome measures. The mean absolute test–retest variability of VT ranged from 12% to 18% across regions. Both DVR-1and SUVR-1 had improved test–retest variability in the range 2%–7%. SUVR-1 was highly correlated with DVR-1 (r2 = 0.97, n = 30). In conclusion, 18F-BCPP-EF has suitable test–retest reproducibility and can be used to quantify MC-I in clinical studies.


2000 ◽  
Vol 20 (6) ◽  
pp. 899-909 ◽  
Author(s):  
Hiroshi Watabe ◽  
Michael A. Channing ◽  
Margaret G. Der ◽  
H. Richard Adams ◽  
Elaine Jagoda ◽  
...  

The goal of this study was to develop a suitable kinetic analysis method for quantification of 5-HT2A receptor parameters with [11C]MDL 100,907. Twelve control studies and four preblocking studies (400 nmol/kg unlabeled MDL 100,907) were performed in isoflurane-anesthetized rhesus monkeys. The plasma input function was determined from arterial blood samples with metabolite measurements by extraction in ethyl acetate. The preblocking studies showed that a two-tissue compartment model was necessary to fit the time activity curves of all brain regions including the cerebellum—in other words, the need for two compartments is not proof of specific binding. Therefore, a three-tissue compartment model was used to analyze the control studies, with three parameters fixed based on the preblocking data. Reliable fits of control data could be obtained only if no more than three parameters were allowed to vary. For routine use of [11C]MDL 100,907, several simplified methods were evaluated. A two-tissue (2T‘) compartment with one fixed parameter was the most reliable compartmental approach; a one-compartment model failed to fit the data adequately. The Logan graphical approach was also tested and produced comparable results to the 2T’ model. However, a simulation study showed that Logan analysis produced a larger bias at higher noise levels. Thus, the 2T' model is the best choice for analysis of [11C]MDL 100,907 studies.


2020 ◽  
Vol 61 (11) ◽  
pp. 1678-1683 ◽  
Author(s):  
Matthew D. Walker ◽  
Andrew J. Morgan ◽  
Kevin M. Bradley ◽  
Daniel R. McGowan

2004 ◽  
Vol 24 (6) ◽  
pp. 600-611 ◽  
Author(s):  
Koichi Sato ◽  
Kiyoshi Fukushi ◽  
Hitoshi Shinotoh ◽  
Shinichiro Nagatsuka ◽  
Noriko Tanaka ◽  
...  

The applicability of two reference tissue-based analyses without arterial blood sampling for the measurement of brain regional acetylcholinesterase (AChE) activity using N-[11C]methylpiperidin-4-yl propionate ([11C]MP4P) was evaluated in 12 healthy subjects. One was a linear least squares analysis derived from Blomqvist's equation, and the other was the analysis of the ratio of target-tissue radioactivity relative to reference-tissue radioactivity proposed by Herholz and coworkers. The standard compartment analysis using arterial input function provided reliable quantification of k3 (an index of AChE activity) estimates in regions with low (neocortex and hippocampus), moderate (thalamus), and high (cerebellum) AChE activity with a coefficient of variation (COV) of 12% to 19%. However, the precise k3 value in the striatum, where AChE activity is the highest, was not obtained. The striatum was used as a reference because its time-radioactivity curve was proportional to the time integral of the arterial input function. Reliable k3 estimates were also obtained in regions with low-to-moderate AChE activity with a COV of less than 21% by striatal reference analyses, though not obtained in the cerebellum. Shape analysis, the previous method of direct k3 estimation from the shape of time-radioactivity data, gave k3 estimates in the cortex and thalamus with a somewhat larger COV. In comparison with the standard analysis, a moderate overestimation of k3 by 9% to 18% in the linear analysis and a moderate underestimation by 2% to 13% in the Herholz method were observed, which were appropriately explained by the results of computer simulation. In conclusion, simplified kinetic analyses are practical and useful for the routine analysis of clinical [11C]MP4P studies and are nearly as effective as the standard analysis for detecting regions with abnormal AChE activity.


2005 ◽  
Vol 26 (1) ◽  
pp. 31-37 ◽  
Author(s):  
Ikuo Yokoyama ◽  
Yusuke Inoue ◽  
Toshiyuki Moritan ◽  
Kuni Ohtomo ◽  
Ryozo Nagai

1989 ◽  
Vol 30 (6) ◽  
pp. 597-601 ◽  
Author(s):  
U. Rudberg ◽  
U. Hesser ◽  
R. Udén

Visceral radiocolloid angiography was performed in 1 230 consecutive patients studied with scintigraphy of the reticuloendothelial system (RES). The hepatic arterial flow was considered increased if an early and obviously increased accumulation of the radiocolloid occurred in the liver during the visceral radionuclide angiography, i.e. that the early part of the liver time-activity curve coincided with the early parts of the kidney and spleen time-activity curves with respect to time and steepness. A generalized increase of arterial blood flow to the liver was found in 70 patients, of whom 54 per cent had alcoholic liver disease, 20 per cent metastatic liver disease, 19 per cent had various diagnoses, and in 7 per cent no certain diagnosis was found. Generalized increase of arterial blood flow to the liver gives a typical appearance in radiocolloid angiography and the corresponding time-activity curves. It may be a sign of severe disease, most often localized in the liver, but in some cases it may be of extrahepatic origin. In 27 per cent it was the only obvious pathologic finding. It was in a few cases a reversible condition. Generalized increase of arterial blood flow to the liver is a clinically important finding that could escape detection if radionuclide angiography is not included in the RES scintigraphy.


2000 ◽  
Vol 12 (2) ◽  
pp. 293-304 ◽  
Author(s):  
Aleksander Kołcz

Similarities between bootstrap aggregation (bagging) and N-tuple sampling are explored to propose a retina-free data-driven version of the N-tuple network, whose close analogies to aggregated regression trees, such as classification and regression trees (CART), lead to further architectural enhancements. Performance of the proposed algorithms is compared with the traditional versions of the N-tuple and CART networks on a number of regression problems. The architecture significantly outperforms conventional N-tuple networks while leading to more compact solutions and avoiding certain implementational pitfalls of the latter.


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