Rapid Quantitative Measurement of CMRO₂ and CBF by Dual Administration of ¹⁵O-Labeled Oxygen and Water During a Single PET Scan—a Validation Study and Error Analysis in Anesthetized Monkeys

Abstract

Cerebral blood flow (CBF) and rate of oxygen metabolism (CMRO 2 ) may be quantified using positron emission tomography (PET) with 15 O-tracers, but the conventional three-step technique requires a relatively long study period, attributed to the need for separate acquisition for each of 15 O 2 , H 2 15 O, and C 15 O tracers, which makes the multiple measurements at different physiologic conditions difficult. In this study, we present a novel, faster technique that provides a pixel-by-pixel calculation of CBF and CMRO 2 from a single PET acquisition with a sequential administration of 15 O 2 and H 2 15 O. Experiments were performed on six anesthetized monkeys to validate this technique. The global CBF, oxygen extraction fraction (OEF), and CMRO 2 obtained by the present technique at rest were not significantly different from those obtained with three-step method. The global OEF (gOEF) also agreed with that determined by simultaneous arterio-sinus blood sampling (gOEF AÀV ) for a physiologically wide range when changing the arterial PaCO 2 (gOEF ¼ 1.03gOEF AÀV þ 0.01, Po0.001). The regional values, as well as the image quality were identical between the present technique and three-step method for CBF, OEF, and CMRO 2 . In addition, a simulation study showed that error sensitivity of the present technique to delay or dispersion of the input function, and the error in the partition coefficient was equivalent to that observed for three-step method. Error sensitivity to cerebral blood volume (CBV) was also identical to that in the three-step and reasonably small, suggesting that a single CBV assessment is sufficient for repeated measures of CBF/CMRO 2 . These results show that this fast technique has an ability for accurate assessment of CBF/CMRO 2 and also allows multiple assessment at different physiologic conditions.

Preserved Acetazolamide Reactivity in Lacunar Patients with Severe White-Matter Lesions: 15O-Labeled Gas and H2O Positron Emission Tomography Studies

“…Patients with lacunar stroke, at least 3 weeks after the onset, were enrolled between April 2009 and April 2010. All patients underwent PET studies with 15 O-labeled gas (C 15 O 2 , 15 O 2 , C 15 O) inhalation and 15 O-water with ACZ challenge autoradiography as described previously (Kudomi et al, 2005(Kudomi et al, , 2007, as well as MRI studies. Lacunar stroke was defined as a typical clinical syndrome associated with a small infarct, < 15 mm in diameter on MRI, restricted to the territory of a perforating artery without adjacent major artery occlusive lesions.…”

“…Quantitative images of CBF and oxygen extraction fraction (OEF) were obtained from a series of PET scans with 15 O-labeled gas (C 15 O 2 , 15 O 2 , and C 15 O) inhalation after a rapid dual autoradiography protocol as reported in a series of publications by Kudomi et al (2005Kudomi et al ( , 2007. Briefly, after a 10-minute transmission scan for the attenuation correction and an 15 O-labeled carbon monoxide (C 15 O) scan for the blood volume assessment, a single dynamic scan was performed for 8 minutes, during which 4,000 MBq of oxygen ( 15 O 2 ) and 5,000 MBq of 15 O-labeled carbon dioxide (C 15 O 2 ) gases were inhaled each > 1 minute, sequentially at an interval of 5 minutes.…”

A Physiologic Model for Recirculation Water Correction in CMRO2 Assessment with 15O2 Inhalation PET

“…The present approach is an extension of a previous study by Iida et al (1993) and Huang et al (1991). It is essential if one intends to apply the rapid 15 O 2 PET technique (Kudomi et al, 2005) to pharmacologic and physiologic stress studies on a wide range of species. Because the PET acquisition period can be prolonged > 3 mins, statistical accuracy can be significantly improved as compared with Ohta et al (1992) and other researchers (Fujita et al, 1999;Vafaee and Gjedde, 2000;Okazawa et al, 2001a, b;Yamauchi et al, 2003;Mintun et al, 2002), under which to avoid effects of RW, the data acquisition period was limited only to < 3 mins (Meyer et al, 1987;Ohta et al, 1992).…”

“…After 3 mins, the monkeys were injected with 370 MBq H 2 15 O for 30 secs by the anterior tibial vein. This was aimed at assessing both CBF and CMRO 2 according to the DARG technique (Kudomi et al, 2005). At 30 secs before inhaling 15 O 2 to the monkeys, arterial blood was withdrawn from the femoral artery for 420 secs at a rate of 0.45 mL/min using a Harvard pump (Harvard Apparatus, Holliston, MA, USA).…”

“…O after DARG protocol (Kudomi et al, 2005) obtained in a monkey study was used. RW TACs were generated from the whole blood TAC by assuming baseline values of k as 0.13, 0.11, 0.34, and 0.73 per min, Dt as 20, 11, 5, and 3 secs, k w as 0.38, 0.43, 0.98, and 0.87 per min, and p as 1.31, 1.01, 0.98, and 0.83, corresponding to humans, pigs, monkeys, and rats, respectively.…”