State of the Art Blood Flow Measurement Technique Inside Human Heart

• Journal List
• Front Physiol
• PMC6593089

Forepart Physiol. 2019; x: 741.

Myocardial Blood Flow and Metabolic Rate of Oxygen Measurement in the Correct and Left Ventricles at Residue and During Practise Using ¹⁵O-Labeled Compounds and PET

Nobuyuki Kudomi,^{1, 2} Kari K. Kalliokoski,¹ Vesa J. Oikonen,¹ Chunlei Han,ⁱ Jukka Kemppainen,^{one, three} Hannu T. Sipilä,¹ Juhani Knuuti,^{1, iii} and Ilkka H. A. Heinonen^{ane, 3, iv, *}

Nobuyuki Kudomi

¹Turku PET Centre, University of Turku, Turku, Republic of finland

ⁱⁱDepartment of Medical Physics, Kinesthesia of Medicine, Kagawa University, Kagawa, Japan

Kari 1000. Kalliokoski

^oneTurku PET Heart, University of Turku, Turku, Finland

Vesa J. Oikonen

¹Turku PET Centre, University of Turku, Turku, Finland

Chunlei Han

¹Turku PET Centre, University of Turku, Turku, Finland

Jukka Kemppainen

¹Turku PET Centre, University of Turku, Turku, Finland

³Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland

Hannu T. Sipilä

¹Turku PET Middle, University of Turku, Turku, Republic of finland

Juhani Knuuti

¹Turku PET Heart, University of Turku, Turku, Finland

³Department of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland

Ilkka H. A. Heinonen

¹Turku PET Centre, University of Turku, Turku, Republic of finland

^threeSection of Clinical Physiology and Nuclear Medicine, University of Turku and Turku University Hospital, Turku, Finland

^ivRydberg Laboratory of Applied Sciences, University of Halmstad, Halmstad, Sweden

Received 2018 Nov 12; Accepted 2019 May 28.

Abstract

Aims: Simultaneous measurement of right (RV) and left ventricle (LV) myocardial claret flow (MBF), oxygen extraction fraction (OEF), and oxygen consumption (MVO₂) non-invasively in humans would provide new possibilities to sympathize cardiac physiology and different patho-physiological states.

Methods: Nosotros developed and tested an optimized novel method to measure MBF, OEF, and MVO₂ simultaneously both in the RV and LV free wall (FW) using positron emission tomography in healthy young men at remainder and during supine bicycle practise.

Results: Resting MBF was not significantly different between the iii myocardial regions. Do increased MBF in the LVFW and septum, merely MBF was lower in the RV compared to septum and LVFW during exercise. Resting OEF was like betwixt the three different myocardial regions (~70%) and increased in response to practise similarly in all regions. MVO₂ increased approximately 2 to three times from rest to exercise in all myocardial regions, just was significantly lower in the RV during practise every bit compared to septum LVFW.

Conclusion: MBF, OEF, and MVO₂ can be assessed simultaneously in the RV and LV myocardia at rest and during exercise. Although there are no major differences in the MBF and OEF betwixt LV and RV myocardial regions in the resting myocardium, MVO₂ per gram of myocardium appears to be lower the RV in the exercising healthy human centre due to lower mean blood flow. The presented method may provide valuable insights for the assessment of MBF, OEF and MVO_ii in hearts in different pathophysiological states.

Keywords: positron emission tomography, myocardial blood flow, myocardial oxygen metabolism, right ventricle, left ventricle

Introduction

Myocardial blood flow (MBF), oxygen extraction fraction (OEF) and metabolic rate of oxygen (MVO₂) may be non-invasively assessed using ¹⁵O-water (H 2 15O) and ^fifteenO-oxygen (¹⁵O_ii) with positron emission tomography (PET) (Iida et al., 1988, 1991, 1992, 1996; Yamamoto et al., 1996; Hermansen et al., 1998). The technique used for MBF and MVO₂ calculation utilizes the unmarried tissue compartment model, and its validity has been confirmed in several studies (Huang et al., 1985; Iida et al., 1988, 1991, 1992, 1996, 2000a; Yamamoto et al., 1996; Hermansen et al., 1998; Choi et al., 1999; Watabe et al., 2005). A unique feature of this technique is that the model incorporates the concept of the perfusable tissue fraction (PTF), which allows correction in MBF and thus as well in MVO_two computation for partial volume outcome (PVE) due to cardiac wall motion and the thin ventricular wall relative to the intrinsic spatial resolution of a PET scanner used (Iida et al., 1988, 1991).

For the left ventricle (LV) myocardium, validated techniques have been published to mensurate MBF and PTF applying dynamic H 2 15O PET scan (Watabe et al., 2005). The MBF measurements of the right ventricle (RV) are challenging with all imaging techniques due to complex shape of the chamber, thin wall, and its rapid motion. A technique to obtain non-invasive and direct measurement of quantitative MBF, PTF, and subsequent OEF and MVO₂ in the RV together with the LV would be of importance, as it could for instance open up new insights for the evaluation of initiation, progression, and effectiveness of the treatments of diverse pathological states that not simply impact LV just as well often the RV (Voelkel et al., 2006). RV coronary perfusion and oxygen consumption are the major determinants of its function (Voelkel et al., 2006), and to the best of our cognition MBF, OEF, and MVO₂ in the human RV have been measured merely in pulmonary hypertensive patients (Bokhari et al., 2011; Wong et al., 2011a,b,c), only never in healthy human subjects and also never simultaneously compared confronting to those of LV. Furthermore, in previous studies analyses to estimate RV blood bend were performed without corrections for PVE and spillover from surrounding myocardium to crenel (Wong et al., 2011a,b,c), which would exist critical sources of possible errors.

Along these lines, the present study aimed to measure MBF, OEF and MVO_ii in healthy human being subjects in LV and RV myocardia simultaneously at rest and during practise by developing a novel assay method, which allows simultaneous computation of MBF and PTF in RV every bit well as LV walls from dynamic H ii 15O PET scan data and also to mensurate OEF and MVO₂ from steady-land ^xvO₂ scan data. Validity of the present method was tested by (1) comparing quantitative MBF values with those by the previous method which practical RV region of interest (ROI) based time action curve (TAC) instead of RV blood TAC (Hermansen et al., 1998), (2) comparison MBF value in LV complimentary wall (FW) myocardium at residual with during supine cycling exercise weather, and (3) comparing PTF obtained from H 2 15O browse data with myocardial extravascular density from transmission scan data (Iida et al., 2000b). The validity was additionally tested by (4) comparison LV and RV blood volume values obtained from the H ii xvO and from C¹⁵O scan data.

Materials and Methods

RV Claret TAC Formula

To obtain the RV blood TAC, ii factors of PVE in RV region of interest (ROI) TAC and spill-over effect from surrounding myocardial wall and adjacent organs are required to exist corrected. Similar to the formulation for LV blood TAC, C _{A, Fifty}(t) (Iida et al., 1988), the formula for venous blood TAC in right ventricle, C _{V, R}(t), was obtained as Equation (5) in the section Appendix A.

Subjects

Healthy young men (northward = fifteen, age xxx ± 5 years, height 179 ± 5 cm, weight 75 ± 7 kg, and maximal oxygen consumption 40 ± 5 mL/kg/min) were studied. The subjects were good for you as determined past health questionnaire and concrete examination by a doctor in addition to pre-ECG and cardiac echocardiography evaluation. The subjects were not nether any medication and were normotensive non-smokers with no history of hypercholesterolemia and no family history of coronary disease. The purpose, nature and potential risks were verbally explained to the subjects before they gave their written informed consent to participate. The report was performed co-ordinate to the Declaration of Helsinki and was canonical past the Upstanding Committee of the Hospital District of South-Western Finland.

PET Experiments

PET acquisition was carried out in 2D style. The PET methods and protocols are explained in particular in our previous study (Heinonen et al., 2014). Briefly, after the transmission browse, scans were undertaken with H 2 fifteenO bolus injection, C^fifteenO inhalation, and ^fifteenO_two continuous inhalation at the resting condition. And then, during exercise with supine cycling (100 Watts), scans with those were repeated. Due to issues in ¹⁵O₂ or C^xvO tracer product, three subjects were missing the ¹⁵O₂ or C¹⁵O scans and the present information are reported in 12 subjects.

Data Processing

Images were reconstructed past the OSEM method using a Hann filter with a cut-off frequency of 4.vi mm. All information sets for aforementioned subjects were resliced using the same prepare of parameters. ROIs were fatigued on LV and RV regions and LV and RV ROI TACs were obtained. ROIs for the left ventricle gratuitous wall (LVFW), septum and RV wall were also fatigued and their TACs were extracted. Then the LV claret TAC, C _{A, L}(t), was estimated using the previous method [Equation (3) in the section Appendix A] (Iida et al., 1988). The RV claret curve, C _{V, R}(t), was estimated past using the present developed formulae [Equation (5) in the section Appendix A].

To generate MBF, PTF, and Five _{B, Fifty} and 5 _{B, R} images with Equation (seven) in the section Appendix B, nosotros applied obtained C _{A, Fifty}(t) and C _{V, R}(t): Due north-method, thus those allow correction for spillover into the LV and RV myocardial walls (Hermansen et al., 1998). Details of the computation method are described in the section Appendix B. Besides, the RV ROI bend instead of C _{V, R}(t) was used for computing the those images: H-method (Hermansen et al., 1998). The blood volume image (Five _B) was besides computed using the C^xvO scan data. The extravascular tissue density (D _ev) [Equation (eight) in the section Appendix B] (Iida et al., 1992), and perfusable tissue alphabetize (PTI) (Iida et al., 1992; Silva et al., 1992; Herrero et al., 1995), are computed using the V _B and reconstructed manual paradigm data. Using the obtained MBF and PTF, then, OEF and MVO_ii in the LVFW, septal and RV wall regions were computed by applying the previously adult formulae (Iida et al., 1996; Yamamoto et al., 1996; Lubberink et al., 2010; Heinonen et al., 2014).

Statistical Assay

Data are shown as mean ± SD across subjects. The Student'south paired t-test was used for the comparison of changes in basic hemodynamical variables from rest to exercise, and comparison between N- and H-methods. Two-way ANOVA for repeated measures was performed to assess the effects of exercise and regional differences in myocardial circulatory variables.

Results

Bones hemodynamic variables at rest and during exercise are shown in Tabular array 1. Exercise increased centre rate, systolic claret pressure, diastolic blood pressure, and thus every bit a result also the mean arterial pressure and rate pressure production.

Tabular array ane

Hemodynamical variables at rest and during practice obtained simultaneously with PET scanning.

	Rest	Exercise
Heart rate (bpm)	68 ± 8	134 ± 16***
BPs (mmHg)	123 ± ix	146 ± xiii***
BPd (mmHg)	72 ± 6	80 ± 12**
MAP (mmHg)	89 ± vii	102 ± 6***

Figure 1 shows representative TACs from LV and RV chamber regions, LV and RV myocardial regions, and estimated C _{A, L}(t) and C _{V, R}(t), respectively. The TACs in the right regions appear before than those in the left, reflecting that H 2 15O was infused into vein and thus firstly passed through RV and and then go on via pulmonary circulation into LV. The estimated RV claret curve, C _{V, R}(t), is higher in scale and less dispersed than left one, C _{A, Fifty}(t).

Estimated left and right ventricle claret curves, extracted left and right ventricle curves, and left and right myocardial activity curves.

Effigy 2 shows a representative view of MBF in one of the subjects at the resting condition by the North- and H-methods. The MBF in LVFW, septal and RV walls tin exist seen in the figure, and the shape and contrast are similar in the LV region between N- and H-methods. Figure three compares PTF images by the N- and H-methods, and D _ev image. The LVFW, septal and RV wall can be seen in the images, and in LVFW region, the shape and contrast are like to those by the H-method, and in RV wall PTF seems lower in H-method. Also, shape in PTF is similar to the D _ev image. Blood volume images are shown in Figure four. The left and right ventricle regions are clearly separated in V _{B, L} and V _{B, R} images. The V _{B, L}+V _{B, R} image by the N-method is similar to the V _B image past the C¹⁵O scan method, however, that seems higher in RV region in the H-method.

Representative view of myocardial claret flow past the nowadays Northward- (A) and previous H-methods (B).

Representative view of perfusable tissue fraction by the nowadays Due north- (A), the previous H-methods (B), and extravascular tissue density D _ev (C).

Representative view of blood volume, by the present N- (A–C), the previous H-methods (D–F), and C15O scan (Thou). The left (B,Eastward) and right (C,F) ventricles are conspicuously separated and the blood book (A) as a sum of (B) and (C) is similar to that by the C15O scan (G).

Quantitative values of MBF, PTF, D _ev, and PTI are summarized in Tabular array 2, those of blood volumes are in Table 3, and OEF and MVO_two in Table 4. The MBF and PTF values based on the N- and H-methods were not significantly different in whatsoever of the myocardial regions. At that place were however significant differences between PTF and D _ev for all regions. Regression analysis showed still correlation between PTF and D _ev for all LVFW (r = 0.71, P < 0.001), septum (r = 0.72, P < 0.001) and RV wall (r = 0.67, P < 0.001) (Figure 5. The corresponding PTI values in resting condition were between 0.vi–0.seven. For the blood book values, there were no significant differences between Northward-method and C^fifteenO scan method, either in LV and RV (Tabular array three).

Table two

Parameters in myocardial region calculated using the North- and H-methods (n = 12).

	Resting status			Exercise condition
	Left	Septum	Right	Left	Septum	Right
MBF (N) (mL/min/g)	0.92 ± 0.24	0.91 ± 0.21	1.07 ± 0.25	2.58 ± 0.55***	2.49 ± 0.38***	1.57 ± 0.threescore##
MBF (H) (mL/min/g)	0.93 ± 0.25	0.92 ± 0.21	1.13 ± 0.26#	2.60 ± 0.52***	2.56 ± 0.40***	1.51 ± 0.56##
PTF (N) (mL/mL)	0.46 ± 0.07†	0.46 ± 0.08†	0.25 ± 0.08###, †	0.38 ± 0.08*, †	0.43 ± 0.11*, †	0.xix ± 0.09*, ### , †
PTF (H) (mL/mL)	0.45 ± 0.07†	0.43 ± 0.09&&,†	0.22 ± 0.08&&, ### , †	0.38 ± 0.08**, †	0.41 ± 0.11*, †	0.xiv ± 0.09*, #### , †
D ev (mL/mL)	0.62 ± 0.07	0.64 ± 0.12	0.49 ± 0.18##	0.62 ± 0.09	0.64 ± 0.09	0.46 ± 0.ten##
PTI (N)	0.68 ± 0.22	0.70 ± 0.44&&&	0.66 ± 0.nineteen&&	0.60 ± 0.10*	0.66 ± 0.22*	0.40 ± 0.eleven*,&&
PTI (H)	0.66 ± 0.22	0.60 ± 0.18	0.55 ± 0.24	0.62 ± 0.12	0.66 ± 0.20**	0.27 ± 0.xv**, ###

Table 3

Claret volume values in ventricle region estimated from the present N- and H- methods, and the C¹⁵O scan method (n = 12).

	Resting condition		Exercise status
	LV	RV	LV	RV
H 2 15O
V B, 50+V B, R (mL/mL) (N)	0.ninety ± 0.03	0.88 ± 0.02&&&	0.93 ± 0.06	0.94 ± 0.06&&&
V B, 50+5 B, R (mL/mL) (H)	0.xc ± 0.03	1.xi ± 0.02†	0.95 ± 0.05	1.23 ± 0.x†
CxvO
VB mL/mL	0.ninety ± 0.05	0.89 ± 0.06	0.93 ± 0.11	0.94 ± 0.11

Table 4

Oxygen extraction fraction (OEF) and myocardial oxygen consumption (MVO₂) in different myocardial regions calculated using the N- and H-methods (north = 12).

	Resting status			Do condition
	Left	Septum	Right	Left	Septum	Correct
N-method
OEF	0.lxx ± 0.08	0.71 ± 0.18&	0.73 ± 0.09&&	0.84 ± 0.14***	0.84 ± 0.10***	0.95 ± 0.06***
MVOtwo (mL/min/grand)	0.xiv ± 0.04	0.13 ± 0.04	0.sixteen ± 0.05	0.44 ± 0.09***	0.44 ± 0.10***	0.30 ± 0.12***, #
H-method
OEF	0.68 ± 0.08	0.76 ± 0.xix	0.88 ± 0.23##	0.84 ± 0.12***	0.93 ± 0.fourteen***,&&&	1.25 ± 0.17***, ## ,&&&
MVO2 (mL/min/grand)	0.fourteen ± 0.04	0.15 ± 0.04	0.21 ± 0.08	0.46 ± 0.eleven***	0.49 ± 0.11***,&&&	0.77 ± 0.77**,&

Linear regressions depicting the correlation between the perfusable tissue fraction (PTF) and the extravascular tissue density (D _ev) values for LV (Fifty), septum (Due south), and RV (R). The solid lines show the regressions.

The MBF was similar in all myocardial regions at rest based on the newly adult Due north-method. Exercise increased MBF significantly in the LVFW and septum, but MBF was significantly lower in the RV as compared to the LVFW and the septum (Tabular array ii). Resting OEF was similar in all regions (Table four) and OEF increased in response to practice in all regions beingness the highest in the RV wall (Tabular array iv). MVO₂ increased two to three times from residuum to exercise, only MVO_ii was significantly lower in the RV as compared to the two other myocardial regions during exercise (Table 4). Finally, myocardial vascular resistance decreased from rest to practice in all ventricular regions (P = 0.01), simply was e'er higher in the RV (127 ± 37 at rest and 109 ± 96 mmHg/mL/min/one thousand during exercise) compared to the LVFW myocardium (101 ± 25 at rest and 61 ± 32 mmHg/mL/min/g during exercise, P = 0.010) and the septum (95 ± 19 at remainder and 72 ± 39 mmHg/mL/min/1000 during exercise, P = 0.015), which did non differ from each other (P = 0.99).

Word

In the present written report, we adult and tested a method which allowed estimating RV blood TAC with taking into business relationship PVE and spillover issue, to simultaneously generate quantitative MBF and PTF images for RV and LV myocardial regions using H 2 15O PET information. Subsequently, OEF and MVO₂ were computed using ^fifteenO₂ PET data applying the obtained MBF and PTF. The present result showed that the MBF values estimated were similar between the nowadays Northward-method and the previously established H-method (Hermansen et al., 1998). The obtained PTF values past the Northward-method were as well similar to those analyzed by the H-method (Hermansen et al., 1998). Comparison in PTF and D _ev by the regression assay showed tight correlations for all LVFW, septal and RV myocardial regions. The obtained claret volume values were not significantly different neither in LV nor RV between by the present N-method and the CO scan method. These findings suggest that the MBF and MVO₂ values for both RV and LV myocardial regions are viable to quantify and assess by the present method, and as such, the method could provide valuable insights for several cardiovascular disease states that affect either both, or primarily the right ventricle (Mertens and Friedberg, 2010).

In the nowadays report, the obtained MBF values past the Northward-method were similar to those analyzed past the H-method (Hermansen et al., 1998), and similar also to the previously obtained mean values ranging from 0.viii to 1.ii mL/min/g in resting condition (Huang et al., 1985; Iida et al., 1988, 1991, 1992, 1996; Silva et al., 1992; Hermansen et al., 1998; Lubberink et al., 2010). Those results indicate the validity of the present MBF computation technique. The obtained PTF values past the N-method in the LVFW were likewise similar to those analyzed past the H-method (Hermansen et al., 1998). For the septal and RV wall region, the PTF values were slighty lower in the H-method simply peculiarly as compared to D _ev (Table two). The difference was likely due to the departure of height between in RV claret TAC and in RV ROI TAC equally shown in Figure 1. RV blood TAC was estimated with taking into account PVE and spillover effect from RV ROI TAC and was thus higher than RV ROI TAC. When RV ROI TAC was applied for the computation, blood volume in the RV was overestimated, existence >1.0 mL/mL and was significantly higher than that obtained by the CO scan method. Afterward, the subtraction on RV blood TAC in RV wall region was excessive, and therefor PTF estimated was smaller. And so the estimated OEF was college than ane in the H-method, which is not physiological. The present North-method OEF and MVO₂ values for the RV myocardium were computed along with the previously demonstrated method adult for LV with applying MBF and PTF (Iida et al., 1996; Yamamoto et al., 1996), implementing correction for the PVE and spillover upshot due to cardiac and respiratory motion, and the thin ventricular wall relative to the intrinsic spatial resolution of a PET scanner used (Iida et al., 1988, 1991). Those facts suggest that when quantitatively imaging the MBF, OEF, and MVO₂ in myocardial region, information technology would be disquisitional to utilise the PVE and spillover effect correction to obtain RV blood bend.

PTF values in the LVFW and septal walls obtained in the report were smaller than those in the previous studies (Iida et al., 1991, 1992, 1996; Hermansen et al., 1998) This could be due to different size of ROI drawn on those regions, namely we intentionally drawn larger size of ROI in LV region in this study for validating MBF computation method in thinner RV wall. When we drew smaller size of ROI in septum region, PTF values estimated were 0.74 ± 0.08 mL/mL which is like to the previous studies (Iida et al., 1991, 1992, 1996; Hermansen et al., 1998). Comparison in PTF and D _ev by the regression assay however showed tight correlations for all LVFW, septal and RV wall: r = 0.87, r = 0.67, and r = 0.56, respectively. The PTF estimates density of myocardium and thus allows the partial volume correction. The D _ev is too a mensurate of density of myocardium [Equation (8) in the section Appendix B] (Iida et al., 1991). We found, notwithstanding, a significant difference between PTF and D _ev, and that the PTI values, which is ratio between them (Iida et al., 1991; Silva et al., 1992; Herrero et al., 1995), were not close to 1.0 simply around 0.7. A previous simulation report demonstrated that the decrease of PTI from 1 to 0.75 is due to heterogeneity and shape of input function (Herrero et al., 1995). Equally mentioned, the size of ROI in the present report was larger and this could accept enhanced the caste of heterogeneity. Those factors may affect the present PTI values to be smaller than 1. As a whole, however, the tight regional correlations and smaller value of PTI identical to the previous sit-in suggest quantitative accuracy of the present approach (Herrero et al., 1995).

For the quantitative computation of MBF in the RV myocardium, awarding of the RV blood TAC subsequently spillover and PVE correction was crucial and the model for the RV blood TAC was obtained by remodeling the previous method for the LV (Iida et al., 1992). The validity of the RV blood TAC was tested past comparing generated V_B in addition to MBF, and PTF equally above. Blood volume in both ventricular regions tin can be conceivably obtained by the C^xvO browse data (Watabe et al., 2005), and that was besides estimated using the H 2 15O scan analysis by Harms et al. (2011). Nosotros also estimated the blood book from the H ii 15O scan information in both LV and RV to test the validity of the present method for the RV blood TAC by comparing the volume between the ii H 2 15O and C^fifteenO methods. The obtained blood volume values were not significantly different neither in LV nor RV. The LV and RV were conspicuously separated in the generated V _{B, L} and Five _{B, R} images, suggesting reliability of the estimated RV blood TAC. A possible method to obtain the right blood TAC could exist to use the RV ROI TAC (Hermansen et al., 1998), however, estimated claret volume in RV was significantly larger than that past the CO scan method, and furthermore the values were larger than i mL/mL (Table iii; Figure iii). Those also suggest that PVE correction is disquisitional for the RV blood TAC, every bit far as a PET scanner with high spatial resolution is not used (Mertens and Friedberg, 2010).

Physiological Considerations

It is very important to brand it possible to measure RV myocardial parameters such as MBF, OEF and MVO₂ non-invasively, considering they are major determinant of RV role (Klima et al., 1999), which in plough is compromised in many patophysiological states (Voelkel et al., 2006). Based on the creature studies, RV MBF is typically 50–90% lower than that in the LV (Zong et al., 2005). In resting swine whose heart would be the closest to homo heart, RV MBF is 70–90% of LV MBF (Duncker and Bache, 2008). All the same, our nowadays PET MBF findings suggest that RV claret flow in humans is similar to that in the LV and septum. However, largely based on canine studies, but also one swine report (Schwartz et al., 1994), ane characteristic of the RV myocardium compared to left one has been considered to be its markedly lower oxygen extraction fraction (40–50%) and subsequent metabolic charge per unit (Klima et al., 1999; Zong et al., 2005; Duncker and Bache, 2008). In contrast, we observed that RV myocardial OEF tended to be higher than that in the LV, especially during exercise. Species difference is the almost likely explanation for this difference. In fact, one previous human PET study has already reported that RV myocardial oxygen extraction appears to be much college than observed in animals (Wong et al., 2011b), although that study was performed in pulmonary hypertensive patients and not in healthy human subjects. The current written report reports for the outset fourth dimension that the normal myocardial oxygen extraction might be higher in salubrious humans than previously institute in beast studies.

It is well-established that RV MBF increases during exercise equally a straight office of heart rate (Klima et al., 1999; Zong et al., 2005). In animal studies it has been institute that RV MBF increases relatively more and tin can even exceed MBF in the LV at heavy practice, as oxygen consumption increases relatively more secondary to the marked increase in pulmonary artery pressure close to maximal do intensity (Klima et al., 1999; Duncker and Bache, 2008). Still, at lower exercise intensities, as likewise practical in the present study, pulmonary pressure remains close to resting values, while LV systolic pressure increases. Theoretically, this physiological background could lead to the situation that MBF, OEF too as MVO_two increase relatively more in the LV than in septal and RV myocardial regions. Interestingly, in accordance with this idea we found in the nowadays study that MVO₂ computed by the newly developed N-method was significantly lower in the RV during exercise as compared to LVFW and septum, due to its lower claret flow. This is also in line with animal studies in which blunted RV myocardial claret flow response and large enhancement in oxygen extraction and consumption has been observed in response to exercise (Klima et al., 1999; Duncker and Bache, 2008). This has been at to the lowest degree in part explained by exaggerated α-adrenergic vasoconstrictor influence on the correct ventricular vasculature (Klima et al., 1999). Interestingly, we also found in the present written report that myocardial vascular resistance was higher in the RV compared to both LV and septal myocardia, which together with lower blood flow and resulting college myocardial blood hateful transit time is plausible mechanism to contribute to higher oxygen extraction in RV especially during exercise (Heinonen et al., 2014). Birthday, every bit the straight sampling of oxygen content in man RV myocardium is extremely difficult, the present technique would allow unique admission to evaluate homo RV blood catamenia and metabolic need quantitatively, and has potential to provide mechanistic insights to numerous pathological states in terms of right ventricle (Iida et al., 2000b; Voelkel et al., 2006).

Limitations

Due to the large corporeality of variables and methods comparisons and thus analyses burden to obtain fifty-fifty these results, merely one researcher observed and analyzed the images. Thus, no intra- or inter-observer variation was documented in the present study, which should be addressed in the future studies. Further, no comprehensive echocardiographic analyses were also performed in the current written report. Information of especially RV wall thicknesses could provide further insights especially in the pathophysiological states on the relation of structural aspects with these PET-derived circulatory and oxygen metabolism related variables.

Summary and conclusions

In decision, this study presents a method to obtain MBF epitome, and OEF and MVO_two values simultaneously for both LV and RV myocardia using H 2 fifteenO and ^fifteenO_ii tracers and PET imaging. In addition we showed that the method developed was feasible in quantitative assessment of MBF, OEF and MVO₂ in humans, at remainder and physiologically challenging do condition. As such, the application of the method and model could provide valuable insights for the assessments of perfusion and various pathological states affecting RV (Mertens and Friedberg, 2010), such equally in pulmonary hypertension, which possesses great challenges for the right ventricle.

Ideals Statement

This study was carried out in accord with recommendations of Ethics Committee of Hospital District of Due south-West Finland with written informed consent from all subjects. All subjects gave written informed consent in accordance with the Proclamation of Helsinki. The protocol was approved Past the Ethics Committee of the Hospital District of South-West Finland.

Author Contributions

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

Conflict of Interest Statement

The authors declare that the research was conducted in the absenteeism of whatever commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

Nosotros thank the technical staff of the Turku PET Center for the efforts and skills defended to this projection.

Glossary

Glossary

MBF	Myocardial blood period
OEF	Oxygen extraction fraction
MVO2	Metabolic rate of oxygen
PET	Positron emission tomography
Htwo 15O	fifteenO labeled h2o
15O2	fifteenO labeled oxygen
PTF	perfusable tissue fraction
PVE	partial volume outcome
LV	Left ventricle
FW	Gratis wall
LVFW	Left ventricle free wall
ROI	region of involvement
TAC	time activity curve
Due north-method	a method for RV-MBF ciphering developed in the present study
H-method	a method for RV-MBF computation adult in the previous study (Hermansen et al., 1998)
C A,Fifty(t)	LV blood TAC
C V,R(t)	the venous claret TAC in right ventricle
C T,R(t)	True myocardial tissue TAC
D R(t)	ROI TAC in the right ventricle (Bq/mL)
D m,R(t)	ROI TAC in RV myocardial region (Bq/mL)
f R	RV myocardial claret flow
βR	recovery coefficient in RV myocardial ROI (0.0 < βR < 1.0)
γR	spillover fraction in RV myocardial ROI (0.0 < γR < i.0)
αR	PTF (m/mL)
D ev	Extravascular tissue density
V B,Fifty	LV blood volume
5 B,R	RV blood volume
V B	Claret volume
PTI	Perfusable tissue index

Footnotes

Funding. The report was conducted within the Center of Excellence in Molecular Imaging in Cardiovascular and Metabolic Inquiry supported by the Academy of Finland, Academy of Turku, Turku University Hospital and Abo University. The written report was further supported by grants from Sigrid Juselius Foundation and JSPS KAKENHI (C), Grant Number 26460728 2014–2016 (NK), The Finnish Cardiovascular Foundation, and The Finnish Diabetes Enquiry Foundation.

References

• Boellaard R., Knaapen P., Rijbroek A., Luurtsema G. J., Lammertsma A. A. (2005). Evaluation of footing function and linear least squares methods for generating parametric claret menstruum images using ^fifteenO-water and Positron Emission Tomography. Mol. Imaging Biol. seven, 273–285. x.1007/s11307-005-0007-2 [PubMed] [CrossRef] [Google Scholar]
• Bokhari Southward., Raina A., Rosenweig East. B., Schulze P. C., Bokhari J., Einstein A. J., et al. . (2011). PET imaging may provide a novel biomarker and understanding of right ventricular dysfunction in patients with idiopathic pulmonary arterial hypertension. Circ. Cardiovasc. Imaging 4, 641–647. x.1161/CIRCIMAGING.110.963207 [PubMed] [CrossRef] [Google Scholar]
• Choi Y., Huang S. C., Hawkins R. A., Kim J. Y., Kim B. T., Hoh C. K., et al. . (1999). Quantification of myocardial blood period using ¹³Due north-ammonia and PET: comparison of tracer models. J. Nucl. Med. 40, 1045–1055. [PubMed] [Google Scholar]
• Duncker D. J., Bache R. J. (2008). Regulation of coronary blood period during exercise. Physiol. Rev. 88, 1009–1086. 10.1152/physrev.00045.2006 [PubMed] [CrossRef] [Google Scholar]
• Harms H. J., de Haan Due south., Knaapen P., Allaart C. P., Lammertsma A. A., Lubberink Chiliad. (2011). Parametric images of myocardial viability using a single ¹⁵O-H₂O PET/CT scan. J. Nucl. Med. 52, 745–749. 10.2967/jnumed.110.085431 [PubMed] [CrossRef] [Google Scholar]
• Heinonen I., Kudomi North., Kemppainen J., Kiviniemi A., Noponen T., Luotolahti Yard., et al. . (2014). Myocardial blood period and its transit time, oxygen utilization, and efficiency of highly endurance-trained human centre. Basic Res. Cardiol. 109:413. 10.1007/s00395-014-0413-1 [PubMed] [CrossRef] [Google Scholar]
• Hermansen F., Rosen Due south. D., Fath-Ordoubadi F., Kooner J. South., Clark J. C., Camici P. Thousand., et al. . (1998). Measurement of myocardial claret flow with oxygen-fifteen labelled water: comparison of unlike administration protocols. Eur. J. Nucl. Med. 25, 751–759. x.1007/s002590050279 [PubMed] [CrossRef] [Google Scholar]
• Herrero P., Staudenherz A., Walsh J. F., Gropler R. J., Bergmann S. R. (1995). Heterogeneity of myocardial perfusion provides the physiological basis of perfusable tissue index. J. Nucl. Med. 36, 320–327. [PubMed] [Google Scholar]
• Huang Southward. C., Schwaiger M., Carson R. E., Carson J., Hansen H., Selin C., et al. . (1985). Quantitative measurement of myocardial blood catamenia with oxygen-15 water and positron computed tomography: an cess of potential and issues. J. Nucl. Med. 26, 616–625. [PubMed] [Google Scholar]
• Iida H., Kanno I., Takahashi A., Miura South., Murakami M., Takahashi One thousand., et al. (1988). Measurement of absolute myocardial claret flow withH 2 15 O and dynamic positron-emission tomography strategy for quantification in relation to the fractional-book effect. Circulation 78, 104–115. 10.1161/01.CIR.78.one.104 [PubMed] [CrossRef] [Google Scholar]
• Iida H., Rhodes C. Thou., Araujo L. I., Yamamoto Y., Silva R., Maseri A., et al. . (1996). Noninvasive quantification of regional myocardial metabolic rate for oxygen by utilise of ¹⁵O_ii inhalation and positron emission tomography. Theory, fault assay, and application in humans. Circulation 94, 792–807. 10.1161/01.CIR.94.4.792 [PubMed] [CrossRef] [Google Scholar]
• Iida H., Rhodes C. M., Silva R., Yamamoto Y., Araujo L. I., Maseri A., et al. . (1991). Myocardial tissue fraction: correction for fractional volume effects and mensurate of tissue viability. J. Nucl. Med. 32, 2169–2175. [PubMed] [Google Scholar]
• Iida H., Rhodes Thousand. C., Silva R., Araujo Fifty. I., Bloomfield P., Lammertsma A. A., et al. . (1992). Employ of the left ventricular time-action curve every bit a noninvasive input function in dynamic oxygen-15-water positron emission tomography J. Nucl. Med. 33, 1669–1677. [PubMed] [Google Scholar]
• Iida H., Tamura Y., Kitamura 1000., Bloomfield P. M., Eberl South., Ono Y. (2000b). Histochemical correlates of ¹⁵O-h2o-perfusable tissue fraction in experimental canine studies of old myocardial infarction. J. Nucl. Med. 41, 1737–1745. [PubMed] [Google Scholar]
• Iida H., Yokoyama I., Agostini D., Banno T., Kato T., Ito K., et al. . (2000a). Quantitative assessment of regional myocardial blood flow using oxygen-15-labelled water and positron emission tomography: a multicentre evaluation in Nihon. Eur. J. Nucl. Med. 27, 192–201. 10.1007/s002590050026 [PubMed] [CrossRef] [Google Scholar]
• Klima U. P., Guerrero J. L., Vlahakes K. J. (1999). Myocardial perfusion and right ventricular function. Ann. Thorac. Cardiovasc. Surg. 5, 74–80. [PubMed] [Google Scholar]
• Koeppe R. A., Holden J. East., Ip W. R. (1985). Performance comparing of parameter estimation techniques for the quantitation of local cerebral blood flow past dynamic positron computed tomography. J. Cereb. Blood Flow Metab. 5, 224–234. 10.1038/jcbfm.1985.29 [PubMed] [CrossRef] [Google Scholar]
• Lubberink M., Harms H. J., Halbmeijer R., de Haan S., Knaapen P., Lammertsma A. A. (2010). Depression-dose quantitative myocardial blood flow imaging using ^xvO-water and PET without attenuation correction. J. Nucl. Med. 51, 575–580. 10.2967/jnumed.109.070748 [PubMed] [CrossRef] [Google Scholar]
• Mertens 50. L., Friedberg 1000. Thousand. (2010). Imaging the correct ventricle–electric current state of the art. Nat. Rev. Cardiol. 7, 551–563. 10.1038/nrcardio.2010.118 [PubMed] [CrossRef] [Google Scholar]
• Schwartz G. G., Greyson C. R., Wisneski J. A., Garcia J., Steinman S. (1994). Relation among regional O₂ consumption, high-free energy phosphates, and substrate uptake in porcine right ventricle. Am. J. Physiol. 266, H521–H530. ten.1152/ajpheart.1994.266.ii.H521 [PubMed] [CrossRef] [Google Scholar]
• Silva R., Yamamoto Y., Rhodes C. G., Iida H., Nihoyannopoulos P., Davies G. J., et al. . (1992). Preoperative prediction of the outcome of coronary revascularization using positron emission tomography. Circulation 86, 1738–1742. 10.1161/01.CIR.86.6.1738 [PubMed] [CrossRef] [Google Scholar]
• Voelkel N. F., Quaife R. A., Leinwand 50. A., Barst R. J., McGoon Thousand. D., Meldrum D. R., et al. . (2006). Right ventricular function and failure: report of a National Centre, Lung, and Claret Institute working group on cellular and molecular mechanisms of correct middle failure. Circulation 114, 1883–1891. ten.1161/CIRCULATIONAHA.106.632208 [PubMed] [CrossRef] [Google Scholar]
• Watabe H., Jino H., Kawachi N., Teramoto N., Hayashi T., Ohta Y., et al. . (2005). Parametric imaging of myocardial blood flow with ¹⁵O-water and PET using the basis function method. J. Nucl. Med. 46, 1219–1224. [PubMed] [Google Scholar]
• Wong Y. Y., Raijmakers P. G., Knaapen P., Lubberink M., Ruiter G., Marcus J. T., et al. . (2011c). Supine-exercise-induced oxygen supply to the right myocardium is attenuated in patients with astringent idiopathic pulmonary arterial hypertension. Heart 97, 2069–2074. 10.1136/heartjnl-2011-300237 [PubMed] [CrossRef] [Google Scholar]
• Wong Y. Y., Ruiter G., Lubberink M., Raijmakers P. G., Knaapen P., Marcus J. T., et al. . (2011b). Right ventricular failure in idiopathic pulmonary arterial hypertension is associated with inefficient myocardial oxygen utilization. Circ. Centre Fail. iv, 700–706. 10.1161/CIRCHEARTFAILURE.111.962381 [PubMed] [CrossRef] [Google Scholar]
• Wong Y. Y., Westerhof Due north., Ruiter G., Lubberink M., Raijmakers P., Knaapen P., et al. . (2011a). Systolic pulmonary artery pressure level and center rate are principal determinants of oxygen consumption in the right ventricular myocardium of patients with idiopathic pulmonary arterial hypertension. Eur. J. Heart Fail. xiii, 1290–1295. 10.1093/eurjhf/hfr140 [PubMed] [CrossRef] [Google Scholar]
• Yamamoto Y., Silva R., Rhodes C. M., Iida H., Lammertsma A. A., Jones T., et al. . (1996). Noninvasive quantification of regional myocardial metabolic rate of oxygen by ¹⁵O₂ inhalation and positron emission tomography. Experimental validation. Apportionment 94, 808–816. x.1161/01.CIR.94.4.808 [PubMed] [CrossRef] [Google Scholar]
• Zong P., Tune J. D., Downey H. F. (2005). Mechanisms of oxygen demand/supply balance in the right ventricle. Exp. Biol. Med. 230, 507–519. x.1177/153537020523000801 [PubMed] [CrossRef] [Google Scholar]

---

Articles from Frontiers in Physiology are provided here courtesy of Frontiers Media SA

---

bensonexced1967.blogspot.com

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6593089/

Share this post