Simulating the effect of cerebral blood flow changes on regional quantification of [<sup>18</sup>F]flutemetamol and [<sup>18</sup>F]florbetaben studies

Heeman, Fiona; Yaqub, Maqsood; Alves, Isadora Lopes; Heurling, Kerstin; Bullich, Santiago; Gispert, Juan Domingo; Boellaard, Ronald; Lammertsma, Adriaan A.

doi:10.1177/0271678x20918029

Cited by 15 publications

(21 citation statements)

References 30 publications

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“…The R 1 also showed a significantly lower value in 18 F-FP-CIT than in 18 F-flutemetamol PET, similar to SUVR, but there was a very strong correlation for most brain regions. The R 1, which represents the delivery rate of radiopharmaceuticals to the regional brain, has recently been used as a proxy for measuring cerebral blood flow in early-phase PET with 18 F-flutemetamol 25 . In the central structures, SUVR showed no significant difference between the two PETs, but R 1 was significantly different.…”

Section: Discussionmentioning

confidence: 99%

“…The second limitation was that we were unable to collect blood samples when acquiring dynamic images due to the retrospective research design. Therefore, we used SRTM, a kinetic model that can be used without blood sampling, which was also used in previous dynamic brain imaging studies 25 , 26 , 30 . In order to obtain results for other kinetic parameters that cannot be obtained from SRTM such as k 1, future studies with blood sampling are warranted.…”

Section: Discussionmentioning

confidence: 99%

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Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated

Yoon

Son

et al. 2021

Sci Rep

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Little is known about whether early-phase PET images of 18F-FP-CIT match those of amyloid PET. Here, we compared early-phase 18F-FP-CIT and 18F-flutemetamol PET images in patients who underwent both within a 1-month interval. The SUVR on early-phase 18F-FP-CIT PET (median, 0.86) was significantly lower than that of 18F-flutemetamol PET (median, 0.91, p < 0.001) for total brain regions including all cerebral lobes and central structures. This significant difference persisted for each brain region except central structures (p = 0.232). The SUVR of total brain regions obtained from early 18F-FP-CIT PET showed a very strong correlation with that of 18F-flutemetamol PET (rho = 0.80, p < 0.001). Among the kinetic parameters, only R1 showed a statistically significant correlation between the two techniques for all brain regions (rho = 0.89, p < 0.001). R1 from 18F-FP-CIT (median, 0.77) was significantly lower in all areas of the brain compared to R1 from 18F-flutemetamol PET (median, 0.81, p < 0.001).18F-FP-CIT demonstrated lower uptake in cortical brain regions than 18F-flutemetamol on early-phase PET. However, both early-phase PETs demonstrated significant correlation of uptake.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated

Yoon

Son

et al. 2021

Sci Rep

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“…In addition, each method provides a unique unit/scale and specific metric for quantification, which motivated inclusion in this review. A key area of current research focusses on the potential sensitivity of visual assessment and quantification methods to variation in scanners [ 101 ], reconstruction algorithms [ 102 – 104 ], scanning time, and scanning window [ 93 , 105 , 106 ], all of which can affect both visual assessment and quantification. See “ Future directions ” later in this review for an overview of ongoing technical validation studies.…”

Section: Quantitative Measures For Clinical Assessment Of Amyloid Burdenmentioning

confidence: 99%

“…Full quantification using dynamic PET acquisition and determination of the non-displaceable binding potential ( BP ND ) were beyond the scope of this review; as such, the methods covered in this review constitute semi-quantification of amyloid PET. Indeed, factors such as acquisition time window and regional cerebral blood flow can impact methods based on static acquisitions, although the latter does not play a major role in an early AD population [ 92 , 93 ]. For a review on the value of full PET quantitation, see Lammertsma [ 94 ].…”

Section: Introductionmentioning

confidence: 99%

Quantification of amyloid PET for future clinical use: a state-of-the-art review

Pemberton

Collij

Heeman

et al. 2022

Eur J Nucl Med Mol Imaging

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Amyloid-β (Aβ) pathology is one of the earliest detectable brain changes in Alzheimer’s disease (AD) pathogenesis. The overall load and spatial distribution of brain Aβ can be determined in vivo using positron emission tomography (PET), for which three fluorine-18 labelled radiotracers have been approved for clinical use. In clinical practice, trained readers will categorise scans as either Aβ positive or negative, based on visual inspection. Diagnostic decisions are often based on these reads and patient selection for clinical trials is increasingly guided by amyloid status. However, tracer deposition in the grey matter as a function of amyloid load is an inherently continuous process, which is not sufficiently appreciated through binary cut-offs alone. State-of-the-art methods for amyloid PET quantification can generate tracer-independent measures of Aβ burden. Recent research has shown the ability of these quantitative measures to highlight pathological changes at the earliest stages of the AD continuum and generate more sensitive thresholds, as well as improving diagnostic confidence around established binary cut-offs. With the recent FDA approval of aducanumab and more candidate drugs on the horizon, early identification of amyloid burden using quantitative measures is critical for enrolling appropriate subjects to help establish the optimal window for therapeutic intervention and secondary prevention. In addition, quantitative amyloid measurements are used for treatment response monitoring in clinical trials. In clinical settings, large multi-centre studies have shown that amyloid PET results change both diagnosis and patient management and that quantification can accurately predict rates of cognitive decline. Whether these changes in management reflect an improvement in clinical outcomes is yet to be determined and further validation work is required to establish the utility of quantification for supporting treatment endpoint decisions. In this state-of-the-art review, several tools and measures available for amyloid PET quantification are summarised and discussed. Use of these methods is growing both clinically and in the research domain. Concurrently, there is a duty of care to the wider dementia community to increase visibility and understanding of these methods.

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“…Both static and dynamic PET image acquisition protocols have been used, where the first is often preferred for routine and multi-centre studies due to its short duration and relatively simple processing. However, a static scan only provides a semi-quantitative measure of amyloid load, which can be affected by confounders [5][6][7][8]. Therefore, performing dynamic acquisitions and full quantification using kinetic modelling may be required for assessing subtle changes in amyloid load, which is of particular importance in longitudinal studies where other physiological parameters may change, thereby introducing bias [5].…”

Section: Introductionmentioning

confidence: 99%

[11C]PIB amyloid quantification: effect of reference region selection

et al. 2020

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Background The standard reference region (RR) for amyloid-beta (Aβ) PET studies is the cerebellar grey matter (GMCB), while alternative RRs have mostly been utilized without prior validation against the gold standard. This study compared five commonly used RRs to gold standard plasma input-based quantification using the GMCB. Methods Thirteen subjects from a test–retest (TRT) study and 30 from a longitudinal study were retrospectively included (total: 17 Alzheimer’s disease, 13 mild cognitive impairment, 13 controls). Dynamic [11C]PiB PET (90 min) and T1-weighted MR scans were co-registered and time–activity curves were extracted for cortical target regions and the following RRs: GMCB, whole cerebellum (WCB), white matter brainstem/pons (WMBS), whole brainstem (WBS) and eroded subcortical white matter (WMES). A two-tissue reversible plasma input model (2T4k_Vb) with GMCB as RR, reference Logan and the simplified reference tissue model were used to derive distribution volume ratios (DVRs), and standardized uptake value (SUV) ratios were calculated for 40–60 min and 60–90 min intervals. Parameter variability was evaluated using TRT scans, and correlations and agreements with the gold standard (DVR from 2T4k_Vb with GMCB RR) were also assessed. Next, longitudinal changes in SUVs (both intervals) were assessed for each RR. Finally, the ability to discriminate between visually Aβ positive and Aβ negative scans was assessed. Results All RRs yielded stable TRT performance (max 5.1% variability), with WCB consistently showing lower variability. All approaches were able to discriminate between Aβ positive and Aβ negative scans, with highest effect sizes obtained for GMCB (range − 0.9 to − 0.7), followed by WCB (range − 0.8 to − 0.6). Furthermore, all approaches provided good correlations with the gold standard (r ≥ 0.78), while the highest bias (as assessed by the regression slope) was observed using WMES (range slope 0.52–0.67), followed by WBS (range slope 0.58–0.92) and WMBS (range slope 0.62–0.91). Finally, RR SUVs were stable across a period of 2.6 years for all except WBS and WMBS RRs (60–90 min interval). Conclusions GMCB and WCB are considered the best RRs for quantifying amyloid burden using [11C]PiB PET.

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Simulating the effect of cerebral blood flow changes on regional quantification of [¹⁸F]flutemetamol and [¹⁸F]florbetaben studies

Cited by 15 publications

References 30 publications

Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated

Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated

Quantification of amyloid PET for future clinical use: a state-of-the-art review

[11C]PIB amyloid quantification: effect of reference region selection

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Simulating the effect of cerebral blood flow changes on regional quantification of [18F]flutemetamol and [18F]florbetaben studies

Cited by 15 publications

References 30 publications

Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated

Early-phase 18F-FP-CIT and 18F-flutemetamol PET were significantly correlated

Quantification of amyloid PET for future clinical use: a state-of-the-art review

[11C]PIB amyloid quantification: effect of reference region selection

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Product

Resources

About

Simulating the effect of cerebral blood flow changes on regional quantification of [¹⁸F]flutemetamol and [¹⁸F]florbetaben studies