with 15O-water in Coronary Artery Disease - Circulationcircimaging.ahajournals.org/content/circcvim/early/2011/09/16/CIRC... · with 15O-water in Coronary Artery Disease ... micro-vascular

Clinical Value of Absolute Quantification of Myocardial Perfusion

with 15O-water in Coronary Artery Disease

Kajander et al: Absolute Quantification of Myocardial Blood Flow

Sami A. Kajander1, MD; Esa Joutsiniemi2, MD; Markku Saraste3, MD;

Mikko Pietilä2, MD, PhD; Heikki Ukkonen2, MD, PhD; Antti Saraste2, MD, PhD;

Hannu T. Sipilä1, PhD; Mika Teräs1, PhD; Maija Mäki3, MD, PhD;

Juhani Airaksinen2, MD, PhD; Jaakko Hartiala3, MD, PhD; Juhani Knuuti1, MD, PhD.

1Turku PET Centre/University of Turku, Finland 2Dept of Medicine/University of Turku, Finland

3Dept of Clinical Physiology and Nuclear Medicine/University of Turku, Finland

Correspondence to: Sami Kajander, MD

Turku PET Centre, PO BOX 52, FI-20521 Turku, Finland. Fax: +358-2-231 8191 Tel: +358-2-313 0000 E-mail: [email protected]

Journal Subject Codes: [124] Cardiovascular imaging agents/Techniques; [29] Coronary imaging: angiography/ultrasound/Doppler/CC; [32] Nuclear cardiology and PET

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Abstract

Background The standard interpretation of perfusion imaging is based on the assessment of

relative perfusion distribution. The limitations of that approach have been recognized in patients

with multi-vessel disease and/or endothelial dysfunction. To date, however, no large clinical

studies have investigated the value of measuring quantitative blood flow, and compared that with

relative uptake.

Methods and Results 104 patients with moderate (30-70%) pre-test likelihood of CAD were

imaged with PET during adenosine stress using 15O-water and dynamic imaging. Absolute

myocardial blood flow was calculated, from which both standard relative myocardial perfusion

images and images that were scaled to known absolute scale were produced. The patients and the

regions were then classified as normal or abnormal and compared against the reference,

conventional angiography with fractional flow reserve. In patient-based analysis, the PPV, NPV

and accuracy of absolute perfusion in the detection of any obstructive CAD were 86%, 97% and

92% with absolute quantification. The corresponding values with relative analysis were 61%,

83% and 73%, respectively. In region-based analysis, the ROC curves confirmed that the

absolute quantification was superior to relative assessment. In particular, the specificity and the

PPV were low using just relative differences in flow. Only 9 of 24 patients with 3-vessel disease

were correctly assessed using relative analysis.

Conclusions The measurement of myocardial blood flow in absolute terms has significant

impact on the interpretation of myocardial perfusion. As expected, multi-vessel disease is more

accurately detected.

Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier:

NCT00627172.

Key Words: cardiac PET, cardiovascular imaging, coronary artery disease, perfusion

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classified as normal or abnormal and compared against t

graphy with fractional flow reserve. In patient-based analysis, h

olute erfusion in the detection of a obstructive CAD were 8

q antification. The corresp nding values with relative analy

classified as normal or abnormal and compared against t

graphy with fractional flow reserve. In patient-based analysis, th

olute perfusion in the detection of any obstructive CAD were 8

quantification. The corresponding values with relative analys



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The detection of functional consequences of epicardial coronary artery disease (CAD) has an

established role in the detection and the guidance of the therapy of the disease (1). In addition,

the assessment of impairment in microcirculatory reactivity has recently gained more interest.

Estimates of myocardial perfusion contain independent prognostic information about future

major cardiac events and the effectiveness of risk reduction strategies (1).

While the standard interpretation of myocardial perfusion imaging is based on assessment of

relative myocardial perfusion defects, this approach has obvious limitations: the assessment is

based on the assumption that the region with the best perfusion is normal, and can be used as a

reference. In clinical scenarios, these shortcomings may arise particularly with patients that have

multi-vessel disease. In addition, global reduction of myocardial perfusion caused by diffuse

micro-vascular disease or balanced multi-vessel disease may be completely missed when

assessment of myocardial perfusion is based on relative uptake of radiotracer.

These limitations may be avoided when using absolute quantification of myocardial blood flow.

At present, the most robust technique to quantify myocardial blood flow non-invasively in

human heart is positron emission tomography (PET). PET is a quantitative technique and allows

fast and effective imaging protocols with relatively low radiation burden in both rest and stress

(2-6).

Absolute quantification of myocardial blood flow with PET is performed using the tracer kinetic

method, which is based on measuring the in vivo kinetics of a tracer concentration during

dynamic acquisition. Normal myocardial blood flow (MBF) at rest is from 0.6 to 1 mL/g/min

and increases by threefold to fivefold in stress as the coronaries dilate (7).

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ease or balanced multi-vessel disease may be completely m

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e. In addition, global reduction of myocardial perfusion cause

ease or balanced multi-vessel disease may be completely m

ardial perfusion is based on relative uptake of radiotracer.



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15O-water and 13N-ammonia are the tracers most widely used for the quantification of myocardial

perfusion with PET. They provide absolute information of MBF over a wide range of blood

flows but their production requires a cyclotron (8). Absolute MBF can, however, also be

assessed with the more widely used generator-produced perfusion tracer 82Rubidium (9).

Despite of this, quantification of MBF with PET has been mainly used in research protocols and

in studies in which absolute perfusion has been measured on the global level only. These studies

have focused on the effect of various risk factors on early coronary dysfunction (10-11). More

recently, due to the increased use of PET (and PET/CT) in clinical cardiology and the

development of analysis methods, simple and robust perfusion quantification has become

available (12-15). However, large patient studies demonstrating the value of absolute

quantification in the detection of CAD - as well as in the guidance of the therapy - are still

largely lacking. In a recent study by Hajjiri et al, 27 patients with known or suspected CAD

were studied. In this material, quantification improved the accuracy for the identification of the

CAD (16).

The aim of the current study was to investigate whether the additional information gained from

absolute quantification of myocardial perfusion has a significant clinical impact in a patient

population with a moderate pre-test probability of CAD.

Methods

General Study Protocol

Initially, 107 consecutive patients with chest discomfort and 30-70% pre-test likelihood of CAD

were enrolled. Prior to invasive coronary angiography, coronary CT angiography followed by

PET perfusion imaging during adenosine stress were performed to 104 of them using 15O water

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a recent study by Hajjiri et al, 27 patients with known or u

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a recent study by Hajjiri et al, 27 patients with known or su

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and dynamic non-gated imaging (GE Discovery VCT PET/CT, General Electric, WI, USA). In 3

subjects, a PET study was not possible due to technical reasons. The main results of hybrid

PET/CT imaging in this population have been published recently (17). As the reference method,

all patients underwent ICA with FFR within two weeks during which no cardiac events took

place. During ICA, FFR measurements were performed for stenoses over 30%. However, there

were some stenoses not subject to FFR because of logistics, the operator’s clinical and visual

assessment of complicated lesions or technical reasons in some extremely tight stenoses.

PET Imaging

Rest-stress perfusion cardiac PET was performed with 900-1100 MBq of 15O-labeled water

(Radiowater Generator, Hidex Oy, Finland) at rest as an intravenous bolus over 15s at an

infusion rate of 10 ml/min. A dynamic non-gated acquisition of the heart 4 min 40 s was

performed (14 x 5 s, 3 x 10 s, 3 x 20 s and 4 x 30 s). After 10 min decay of the radioactivity, an

adenosine-induced stress scan was performed. Adenosine was started 2 minutes before the scan

start and infused at 140 μg/kg body weight/min (17).

ICA and FFR

All coronary angiographies were performed on Siemens Axiom Artis coronary angiography

system (Siemens, Germany). Quantitative analysis of coronary angiograms (QCA) was

performed using software with automated edge detection system (Quantcore, Siemens, Germany)

by an experienced reader (MP) blinded to other the results of PET, CTA and FFR. 17 standard

segments were analyzed.

In the presence of 30%-70% stenosis, FFR measurement was performed using ComboMap®

pressure/flow instrument and a 0.014-inch BrightWire® pressure guidewires (Volcano

Corp.,USA). The pressure was measured distally to the lesion during maximal hyperemia

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ml/min. A dynamic non-gated acquisition of the heart 4 m

, 3 x 10 s, 3 x 20 s and 4 x 30 s). After 10 min decay of the r d

stress scan was rformed. Adenosine was started 2 minutes be

140 μg/kg body weight/min (17).

ml/min. A dynamic non-gated acquisition of the heart 4 m

, 3 x 10 s, 3 x 20 s and 4 x 30 s). After 10 min decay of the rad

stress scan was performed. Adenosine was started 2 minutes be

140 μg/kg body weight/min (17).



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induced by 18 μg intracoronary boluses of adenosine with simultaneous measurement of aortic

pressure through the catheter. FFR was calculated as the ratio between mean distal pressure and

mean aortic pressure (18-20).

Analysis and Interpretation of the Studies

The perfusion studies were analyzed using validated software. First, absolute blood flow for the

standard 17 myocardial segments were calculated using a standard anatomical template and

CarimasTM software (14,17) (www.turkupetcentre.net/carimasturku). The PET images were fused

with corresponding CTA images at a GE ADW Workstation (CardIQ Fusion, GE Healthcare, USA)

to determine the individual regions supplied by each artery. Absolute myocardial flow in any region

of less than 2.5 mL/g/min during stress was considered abnormal (17).

In patient based analysis the result was interpreted as pathological if any region showed abnormal

perfusion.

Although it is customary in clinical practice to evaluate relative perfusion abnormalities visually,

we chose to use calculated MBF values as the basis of the relative uptake analysis, too. The

region of the highest perfusion (regardless of the absolute flow) was assigned the value “1” after

which all the other areas were graded relative to that. For example, if the MBF were 2.0

mL/g/min in the LAD territory, 1.5 mL/g/min in the LCX territory and 1.0 mL/g/min in the

RCA-supplied area, the corresponding relative values were 1, 0.75 and 0.5. The optimal cut-off

for the relative uptake was 0.8 (i.e., 80% of the maximal uptake in any region) on the basis of the

ROC curve.

Parametric images of the blood flow were produced from the data. The scaling of the images was

either automatic (with relative scale the best perfused region always has the brightest color

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alysis the result was interpreted as pathological if any region shalysis the result was interpreted as pathological if any region sh



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regardless of the actual blood flow and the other regions have colors reflecting the flows relative to

the best region) or manual (with absolute scale the flow in ml/g/min relates to a predefined color).

When FFR was performed during ICA, stenoses with FFR >0.8 were classified as non-

significant (20), regardless of the degree of narrowing. In cases without FFR, luminal diameter

narrowing 50% in QCA was considered significant.

Statistical Methods

Sensitivity, specificity, PPV, NPV and accuracy were calculated for both quantitative blood flow

and quantitative relative uptake. ROC analysis curves were performed with the Youden index

and the areas under the curves were calculated. McNemar`s test was performed to compare

accuracy of quantitative blood flow and quantitative relative uptake against reference method

(ICA with FFR). A P-value of < 0.05 was considered statistically significant. The statistical tests

were performed with SAS version 9.1.

Results

According to the reference method (ICA with FFR), 38/104 patients that underwent PET had

significant CAD. Two of the three patients without PET data had significant CAD but were not

included in the analysis. Of the 38 patients, 24 had multi-vessel disease and 14 had single-vessel

disease. 18 patients had either a totally occluded vessel or >90% stenosis in which FFR was not

technically possible. In four other patients FFR could not be performed because of scheduling or

technical reasons. 238/312 arteries were normal or had non-significant disease, 74 were

significantly diseased.

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ative blood flow and antita ive relative u ake ainst refer

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ative blood flow and quantitative relative uptake against refer

P-value of < 0.05 was considered statistically significant. The sd

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Patient-based analysis

Quantitative blood flow analysis correctly identified 36 out of the 38 positive patients. There

were two false negatives in which the flow was 2.5mL/g/min in all regions and 6 false

positives. Of these, 5 patients had diffusely reduced flow whereas one patient had <2.5mL/g/min

flow in just one vascular region. Quantitative analysis resulted in sensitivity of 95%, specificity

91%, PPV 86% and NPV 97%.

With relative myocardial uptake analysis, PET was able to identify only 28/38 patients with

significant CAD correctly. There were 10 false negatives and 18 false positives. This resulted in

sensitivity of 74% and specificity of 73%. PPV and NPV were 61% and 83%, respectively. The

results of the patient-based analysis are exhibited in Tables 1-2 and Figure 1.

Patients with multi-vessel disease

There were 24 patients with significant multi-vessel disease. All but one (which was a false

negative) were identified by abnormal quantitative blood flow. In addition, there were 5 false

positives with diffusely reduced MBF but no CAD according to ICA/FFR.

Using relative uptake, we were able to detect 22 of the 24 patients as having significant CAD

whereas 2 patients were erroneously interpreted as being normal (both had very low but diffusely

reduced flow). In addition, 26 patients were classified as having multi-vessel disease although

they did not. The results of the analysis of patients with multi-vessel disease are presented in

Figures 2a and 2b.

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t-based anal sis are exhibited in Tables 1-2 and Fi re 1.

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ents with sig ificant multi-vessel disease. All but one (whi h

t-based analysis are exhibited in Tables 1-2 and Figure 1.

i-vessel disease

ents with significant multi-vessel disease. All but one (which



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Regional analysis

In regional (vessel-based) analysis quantitative blood flow had the sensitivity and the specificity

of 95% and 92%, respectively for in the detection of significant CAD. PPV, NPV and accuracy

were 78%, 98% and 92%, respectively. When relative flow analysis was used, PPV, NPV and

accuracy were 64%, 85% and 82%, respectively. The results of the two analysis methods were,

in addition, compared by means of ROC analysis. The area under the curve was 0.94

(quantitative blood flow) and 0.73 (relative uptake).

The relative perfusion method failed to assess the underlying extent of the disease in 13/24

patients with multi-vessel CAD because they were thought to have one-vessel disease only. In

addition, 7 other patients with the diagnosis of multi-vessel disease really had one-vessel disease.

The region-based results are presented in Tables 3-4 and Figures 2-3.

Discussion

Myocardial perfusion yields independent and important information about risk stratification in

patients with CAD. In the present study, we compared the conventional approach of assessing

relative radiotracer uptake to quantitative measurement of MBF and found out that the latter

method was more sensitive and accurate. In particular, in the presence of the multi-vessel disease

relative differences in regional myocardial radiotracer uptake may underestimate the severity of

CAD.

There are three main patient groups that account for the differences between relative uptake and

quantitative blood flow. First group is the patients with three-vessel disease and balanced,

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ssults are presented in Tables 3-4 and Figures 2-3.



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uniform reduction of perfusion. In this study, using relative uptake analysis only, we would have

totally missed CAD in two such patients. Using absolute quantification, however, balanced CAD

is usually easily distinguished from normal perfusion.

The second major group of discrepant findings consisted of 13 other patients with multi-vessel

disease. In these patients, presence of CAD was detected using relative uptake analysis but only

one region was considered pathological. This, too, is easy to understand because the region with

the best perfusion is considered to represent normal flow in relative analysis - which is however

not usually the case in patients with multi-vessel disease.

The third group of discrepancies consisted of patients with high MBF but inhomogeneous

radiotracer uptake erroneously interpreted as perfusion defects. According to ICA and FFR, these

patients had no significant CAD. Such misinterpretation is most likely to occur with tracers with

linear relationship between the measured and actual flow even at high range, such as 15O-water,

but may also be important with other tracers with high extraction (21). This potential pitfall is

avoided when using quantitative blood flow analysis.

Two case examples of false findings in relative uptake and their counterpart images based on the

quantitative blood flow are shown in Figures 4 and 5.

An interesting subgroup is the patients with normal (or nearly normal) epicardial vessels but with

diffusely reduced MBF. With quantitative PET, these patients with possible microcirculatory

disease often cannot be separated from those with epicardial multi-vessel disease. This may have

important implications on decisions concerning referral to invasive coronary angiography but it

should be noted that such patients can usually be correctly diagnosed with hybrid PET/CT

imaging. On the other hand, relative perfusion method frequently classifies these patients as

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rroneousl inter eted as rfusion defects. Accordi to ICA n

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portant with other tracers wit high extraction (21). This pot

rroneously interpreted as perfusion defects. According to ICA an

ificant CAD. Such misinterpretation is most likely to occur wit

etween the measured and actual flow even at high range, such

portant with other tracers with high extraction (21). This pote



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normal. Of course, the relative quantity of patients with multi- and single vessel disease as well

as impaired microcirculation reflects a particular patient population and the pre-test probability

of CAD in that group.

We utilized hybrid PET/CT images to visualize the location of the actual coronary arteries and

their territories. The normal variation in anatomy is considerable and possible “non-anatomical”

pseudo lesions in perfusion images are more easily distinguished from real abnormalities. In our

opinion, it is advisable to utilize hybrid images for anatomy and flow values for function if both

are available.

A limitation of the current study is that the poor performance of relative uptake analysis at high

perfusion range should not be directly extrapolated to other perfusion tracers used in PET

imaging or conventional nuclear medicine. Most tracers (such as sestamibi, tetrofosmin,

ammonia and rubidium) exhibit non-linear flow characteristics between detected signal and

actual perfusion, thus naturally omitting heterogeneity in perfusion at the high end of the normal

perfusion range. These relationships are demonstrated in Figure 6 (22).

Another limitation is the lack of ECG-gating in our approach. Gated images provide information

about wall motion and this information could improve the accuracy of relative analysis. A third

limitation of the study is the relatively small number of patients with significant CAD (n=38).

This reflects the patient population but warrants further studies with more patients. On the other

hand this kind of population with intermediate likelihood of disease should be ideal for assessing

diagnostic methods especially since we avoided referral bias by performing ICA in all patients.

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ould not be directl extra lated to other rfusion tracers

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us naturally omitting heterog neity in perfusion at the high end

ould not be directly extrapolated to other perfusion tracers

ntional nuclear medicine. Most tracers (such as sestamibi,t

dium) exhibit non-linear flow characteristics between detecte

us naturally omitting heterogeneity in perfusion at the high end



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Conclusion

Quantification of myocardial blood flow is superior to the assessment of relative uptake only. In

particular, assessment of the absolute flow improves the correct detection of multi-vessel disease.

In addition, patients with diffusely reduced flow but with no significant epicardial stenoses are

easily identified using quantification. Furthermore, local variances within normal high flow can

be separated from regionally compromised perfusion. This is particularly important when tracers

with high extraction are used.



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Acknowledgements

We warmly thank Ville Aalto for his skillful statistical analysis. This study was conducted within

the Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research,

supported by the Academy of Finland, University of Turku, Turku University Hospital, and Abo

Academy. Financial support was also obtained from the Finnish Cardiovascular Foundation and

the Hospital District of Southwest Finland.

Disclosures

None.



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20. Pijls NH. Optimum guidance of complex PCI by coronary pressure measurement. Heart.

2004; 90:1085-1093.

21. Nekolla SG, Reder S, Saraste A, Higuchi T, Dzewas G, Preissel A, Huisman M, Poethko

T, Schuster T, Yu M, Robinson S, Casebier D, Henke J, Wester HJ, Schwaiger M.

Evaluation of the novel myocardial perfusion positron-emission tomography tracer 18F-

BMS-747158-02: comparison to 13N-ammonia and validation with microspheres in a pig

model. Circulation. 2009;119:2333-42.

22. Knuuti J, Kajander S, Mäki M, Ukkonen H. Quantification of myocardial blood flow will

reform the detection of CAD. J Nucl Cardiol. 2009;16:497-506.



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Table 1. Analysis of quantitative blood flow, results per patient

N=104

ICA + FFR

+

-

+

36

6

PETwith quantitative blood flow

-

2

60

Table 2. Analysis of relative uptake, results per patient

N=104

ICA + FFR

+

-

+

28

18

PETwith relative uptake

-

10

48

f relative uptake, results per patient f relative uptake, results per patient

ICA + FFR

+ -



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Table 3. Analysis of quantitative blood flow, results per region

N=312

ICA + FFR

+

-

+

70

20

PETwith quantitative blood flow

-

4

218

Table 4. Analysis of relative uptake, results per region

N=312

ICA + FFR

+

-

+

34

19

PETwith relative uptake -

40

219

+

f relative uptake, results per region

ICA + FFR

+



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Figure Legends

Figure 1. Patient-based assessment: Quantitative blood flow vs. relative uptake in adenosine-

induced stress with ICA+FFR as reference method. Normal flow: 2.5 mL/g/min in quantitative

blood flow, 80% of the maximal uptake in relative uptake. Quantitative blood flow (blue bar).

Relative uptake (burgundy bar). N=104.

Figure 2a. Regional (per-vessel) assessment: Quantitative blood flow vs. relative uptake in

adenosine-induced stress with ICA+FFR as reference method. Normal flow: 2.5 mL/g/min in

quantitative blood flow, 80% of the maximal uptake in relative uptake. Quantitative blood flow

(blue bar). Relative uptake (burgundy bar). N=312.

Figure 2b. Regional (per-vessel) assessment in patients with multivessel disease: Quantitative blood

flow vs. relative uptake in adenosine-induced stress with ICA+FFR as reference method. Normal

flow: 2.5 mL/g/min in quantitative blood flow, 80% of the maximal uptake in relative uptake.

Quantitative blood flow (blue bar). Relative uptake (burgundy bar). N=312.

Figure 3. ROC curves of regional assessment methods: Quantitative blood flow vs. relative uptake.

Solid blue line: quantitative blood flow. Dotted red line: relative uptake.

Figure 4. False positive finding in relative uptake analysis. Figure 4a: Relative uptake in hybrid

PET/CTA-images, automatic color scale. The heterogeneity in perfusion was erroneously

interpreted as reduced perfusion in LAD and LCX territories. Normal perfusion: yellow or red

color, reduced perfusion: green or blue color. Figure 4b: Quantitative blood flow with a preset color

mmallllllal f f f f f f flololololololow:w:w:w:w:w:w: 2.2.2.2.2.2.2.5 5 5 5 5 5 5 mmmmmmm

ow, 80% of the maximal uptake in relative uptake. Quantitativ

(per-vesse ) assessment in patients with multivessel disease: Qu

ow, 80% of the maximal uptake in relative uptake. Quantitativ

uptake (burgundy bar). N=312.

(per-vessel) assessment in patients with multivessel disease: Qu



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scale of 0-3.5 mL/g/min. Normal perfusion is 2.5 mL/g/min (yellow or red color). Reduced

perfusion is < 2,5 mL/g/min (green or blue color). Normal finding. ICA + FFR was normal.

Figure 5. False negative finding in relative uptake analysis. Figure 5a: Relative uptake in hybrid

PET/CTA-images, automatic color scale. This appeared normal in all regions and was false

negative finding. Normal perfusion: yellow or red color, reduced perfusion: green or blue color.

Figure 5b: Quantitative blood flow images with a preset color scale of 0-3.5 mL/g/min. Normal

perfusion is 2.5 mL/g/min (yellow or red color). Reduced perfusion is < 2,5 mL/g/min (green or

blue color). Blue color reflects severely impaired perfusion in all 3 major vascular territories. ICA +

FFR was abnormal in all 3 vessels.

Figure 6. Graphical presentation of the relationship between absolute myocardial perfusion and

tracer uptake. The lines are estimates of the tracer uptake characteristics. In all tracers except 15O-

water, tracer extraction is reduced when perfusion is increased. Reproduced with permission (ref:

Knuuti J, Kajander S, Mäki M, Ukkonen H. Quantification of myocardial blood flow will reform

the detection of CAD. J Nucl Cardiol. 2009;16:497-506.)

p esentation of the relationshi between absolute ocardial e

nes are estimates of the tracer uptake characteristics. In all trace

i

S, Mäki M, Ukkonen H. Quantification of my cardial blood fl w

presentation of the relationship between absolute myocardial pe

nes are estimates of the tracer uptake characteristics. In all trace

ion is reduced when perfusion is increased. Reproduced with pe

S, Mäki M, Ukkonen H. Quantification of myocardial blood flow



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Figure 1: Patient Analysis against ICA+FFR

0

20

40

60

80

100

%

quantitative blood f low 95 91 86 97 92

relative uptake 74 73 61 83 73

Sensitivity (%) Specif icity (%) PPV (%) NPV (%) Accuracy (%)



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Figure 2a: Regional (Per-Vessel) Analysis against ICA+FFR

0

20

40

60

80

100

%






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Figure 2b: Regional (Per-Vessel) Analysis in Patients with Multi-Vessel Disease against ICA+FFR

0

20

40

60

80

100

%






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Area under the ROC Curve: Quantitative flow: 0.94 (Solid blue line)Relative uptake: 0.73 (Dotted red line)



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Hannu T. Sipilä, Mika Teräs, Maija Mäki, Juhani Airaksinen, Jaakko Hartiala and Juhani KnuutiSami A. Kajander, Esa Joutsiniemi, Markku Saraste, Mikko Pietilä, Heikki Ukkonen, Antti Saraste,

Artery DiseaseO-water in Coronary15Clinical Value of Absolute Quantification of Myocardial Perfusion with

Print ISSN: 1941-9651. Online ISSN: 1942-0080 Copyright © 2011 American Heart Association, Inc. All rights reserved.

TX 75231is published by the American Heart Association, 7272 Greenville Avenue, Dallas,Circulation: Cardiovascular Imaging

published online September 16, 2011;Circ Cardiovasc Imaging.

http://circimaging.ahajournals.org/content/early/2011/09/16/CIRCIMAGING.110.960732World Wide Web at:

The online version of this article, along with updated information and services, is located on the

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is online at: Circulation: Cardiovascular Imaging Information about subscribing to Subscriptions:

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can be obtained via RightsLink, a service of the Copyright Clearance Center,Circulation: Cardiovascular Imaging Requests for permissions to reproduce figures, tables, or portions of articles originally published inPermissions:



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