Perfusion imaging

Technetium-9 9m sestamibi is used in myocardial perfusion imaging for the evaluation of ischemic heart disease. It is prepared from a lyophilized kit containing tetrakis(2-methoxy isobutyl isonittile) copper(I) tetrafluoroborate stored under nitrogen. Upon reconstitution with up to 5.6 GBq (150 mCi) of 99mTc pertechnetate, the product is formed by boiling for 10 minutes. 

By far, the most widely used and most empirically studied tissue viability imaging techniques are those that study tissue perfusion, and discussion of perfusion imaging techniques will dominate this section. We will also mention a few emerging techniques that currently are not as widely used in the acute stroke setting, but show promise for the future. 

Perfusion imaging techniques study pathophysiologic events that occur in capillaries and other microscopic blood vessels that cannot be seen by angiographic techniques like CTA or MRA. The perfusion imaging techniques in most widespread clinical use are performed using CT or MRl, and generally obtain or... 

Qualitative analysis of perfusion images is usually based on two assumptions that are derived from the pathophysiologic principles discussed above. First, tissue with visibly decreased CBV is so severely ischemic that it is unlikely to survive and lies within the core of the infarct. Second, tissue with decreased CBF or prolonged MTT may be mildly or severely ischemic and may or may not be salvageable. If this tissue does not appear abnormal in another, more specific type of image (such as CBV or DWI), it represents the ischemic penumbra and may potentially be rescued by immediate therapy. 

Gillard JH, Antoun NM, Burnet NG, Pickard JD. Reproducibility of quantitative CT perfusion imaging. Br J Radiol 2001 74 552-555. 

Stress myocardial perfusion imaging with the radionuclides technetium-99m sestamibi or thallium-201 allows for the identification of multivessel disease and assessment of myocardial viability. 

Before complexes can be used in nuclear medicine, especially for brain function studies, in vivo reactivity has to be imposed upon them. Retention in the brain is necessary for perfusion imaging. This can be achieved by substituents on the ligand that bind them to binding sites in the brain. N-alkylation with methyl and other alkyl groups led to the class of complexes shown in Fig. 19. Upon complexation to technetium, the IV-alkyl substituent can assume a syn or anti configuration with respect to the oxo ligand, as proved by X-ray crystal... 

Fig. 4. Lipophilic-cationic( +1) myocardial perfusion imaging agents A) 99mTc-tetrofosmin R = -CH2CH,0CH,CH3 B), 9"Tc = sestamibi R=C=NCH,C (OCHJ (CH,), Q 99mTc-furifosmin R = -CH2CH2OCH2CH3...

Complex 61 (99mTc(V)-D,L-HM-PAO, Ceretec) is an approved cerebral perfusion imaging agent for evaluation of stroke. The tetradentate... 

The lipophilic complex 99mTc(IV)-L,L-ECD (62) with a deprotonated L,L-ethylcysteine dimer as ligand, is clinically used as a cerebral perfusion imaging agent. It crosses the blood-brain barrier and... 

Fig. 10. X-ray crystal structure of the cerebral perfusion imaging agent 61 (Ceretec) the D,L-form of ligand HM-PAO is used. Adapted from (275).

Complex 65 (Cardiolite), 99mTc(I)-sestamibi, is used for myocardial perfusion imaging. It was designed on the basis that lipophilic cationic complexes behave as potassium mimics and are taken up by the myocardium (281). The sequential metabolism of the six methoxy groups of 65 to hydroxyl groups in the liver leads to formation of 99mTc complexes with greater hydrophilicity which are not retained in myocardial tissues (282). 

Detre JA, Leigh JS, Williams DS, Koretsky AP (1992) Perfusion imaging. Magn Reson Med 23(1) 37 5... 

Many studies have been performed in order to compare the mode of action, and retention kinetics in the myocardium, and the way of excretion of these different cationic species for both cell cultures, as well as in whole heart preparations. Even Tc NMR spectroscopy has been used to characterize in vivo the nature of the compounds for sestamibi (see Section 5.2.2.10.1). A recent comparative kinetic study between the different cations can be taken as a base for the clinical interpretation of the different perfusion imaging findings. ... 

Brain imaging has become a major goal of Xc coordination chemistry, both for perfusion imaging and, more recently, for the labeling of so called central nervous system (CNS) receptor... 

Figure 2.1 illustrates normal myocardial perfusion by PET using Rubidium ( Rb) at rest and after dipyridamole stress in 3D views. A coronary arterial map is overlaid on the perfusion image or alternatively an arterial distribution map as a precise perfusion atlas of the coronary artery tree and all its secondary and tertiary branches [25]. 

In Fig. 2.2, the PET perfusion images show severe stenosis or occlusion of the left circumflex (LCx) and right (RCA) coronary arteries with a moderately severe stenosis of the left anterior descending (LAD) coronary artery proximal to its second diagonal branch. The ejection fraction (EF) and regional LV contraction were normal. Therefore, this example illustrates purely ischemic myocardium without scar and without injured or poorly contracting myocardium. 

Fig. 2.2 Positron emission tomography (PET) perfusion images showing severe stenosis/ occlusion of the left circumflex (LCx) and right (RCA) coronary arteries with...

Indications for radionuclide imaging in these patients are detailed in current ACC/AHA guidelines [68] and ACCF/ASNC appropriateness criteria for SPECT myocardial perfusion imaging [69]. While a detailed discussion of these indications is beyond the purpose of this text, for patients with advanced... 

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