Abstract:

Introduction: the role of intracerebral stenosis of brain arteries in the development of postoperative strokes in patients with extensive atherosclerosis remains unresolved, and in clinical practice, magnetic resonance angiography (MRA) of cerebral arteries is not carried out routinely to predict the risk of postoperative cerebrovascular disorders.

Aim: was to identify factors of MRA of intracerebral arteries essential for prognosis of ischemic strokes in postoperative period of angiosurgical interventions and in acute period of myocardial infarction (AMI), from the quantitative processing of brain MRA recruited from the MRI — MRA register.

Materials and methods: results of brain MRA of 195 patients with extensive atherosclerosis carried out before cardio- or angiosurgical interventions were analyzed. Of these, three had an ischemic stroke after carotid endarterectomy, three — after CABG operations, and five — after surgical treatment of thoracic aortic aneurysms, on 2-5 day after surgery. We also studied results of brain MRA in five patients who developed an episode of ischemic brain stroke in the acute period of acute myocardial infarction. In all cases of circulatory disorders were localized in the region of middle cerebral artery (MCA). Everyone was given a time-of-flight MRA with reconstruction of three-dimensional anatomical picture of cerebral arteries. The index of gradient of narrowing of arterial lumen (GNL) of artery was calculated as the ratio of the difference in the area of artery at stenosis and at nearest proximal non-stenosed level, to the distance between them, along the course of the vessel: GNL={(Snorm–Sstenosis)/Dnorm–stenosis}, mm²/mm.

Results: analyzing the visual picture of brain MRA in patients, the sign of critical narrowing of MCA for >50% was observed in all five patients with acute ischemic stroke concomitant with acute myocardial infarction. In all 11 patients who developed postoperative stroke, the visual picture of MCA stenosis was bilateral, more pronounced on the side of the ischemic disorder after the operation. When using the GNL index, it was obvious that ischemic stroke developed only when the stenosis was more sharp than GSP >1,05 mm²/mm. Of five patients who showed signs of MCA stenosis but did not have postoperative stroke, four took doses of 250 mg/day or more of ethylmethylhydroxypyridine succinate (mexidol) for more than a month at the outpatient stage. The sensitivity of MRA preoperative sign of MCA stenosis in relation to postoperative ischemic stroke was 100% in all groups, the specificity and diagnostic accuracy was 97,5%, the predictability of a positive conclusion was 62,5-75%, and the predictability of a negative conclusion was 97-99%.

Conclusion: technology for evaluating the gradient of narrowing of arterial lumen in the area of atherosclerotic stenosis of intracerebral arteries in patients with extensive atherosclerosis allows predicting the risk of postoperative stroke. Gradient of narrowing of arterial lumen index for atherosclerotic middle cerebral artery over 1,05 mm²/mm in patients with extensive atherosclerosis predicts increased risk of strokes in postoperative period, or as a complication of acute myocardial infarction. Long-term preoperative injection of mexidol probably reduces the risk of postoperative stroke in extensive atherosclerosis.

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Abstract:

Aim: was to make preclinical and imaging tests of the trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (DCTA) complex as a universal contrast agent for MRI and single-photon emission imaging, with Mn (Cyclomang) and ^99mTc- (Cyclotech), respectively.

Material and Methods: the complex of trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid (DCTA) was synthesized at the department of organic chemistry of National Research Tomsk Polytechnic university, using the original technology in the nanopowder phase using manganese (II) carbonate, or generator eluate ^99mTc, and NaH₂DCTA, resulting in a 0.5 M solution of Мn-DCTA or ^99mTc-DCTA. LD50 values were determined in experiments on laboratory mice. A visualization study was performed in 4 cats and 3 dogs with malignant neoplasms of chest organs and in one dog with a tumor of the left pontocerebellar angle. All of them underwent consecutively MRI with contrast enhancement with Mn-DCTA and SPECT - with ^99mTc-DCTA.

Results: for Cyclotech LD50 >18/ml/kg, for 0.5 M Mn-DCTA (Cyclomang) solution, the LD50 index significantly exceeds 16.9 ml/kg BW. Changes in the content of manganese in the blood plasma of rats when they were administered Mn-DCTA, did not occur. LD50 values allow us to assign the drug in accordance with Russian regulation GOST 12.1.007-76. to group 4 (low-hazard substances). In both cases, in the range of physiological pH, the thermodynamic stability constant is >19.3. In studies in animals with MRI, the enhancement index of T1-weighted spin-echo image of the tumor in all cases exceeded 1.7 (mean 1.82±0.10). When calculating the «tumor/back-ground» index for ^99mTc-DCTA, it was 2.6-7.3 (mean 4.12±1.05).

Conclusion: DCTA complexes with manganese (II) - for enhancement in MRI and with ^99mTc- for SPECT- have very close pharmacokinetic properties, are non-toxic, do not dissociate in physiological environments and can be further used for contrast enhancement in multimodal MRI-SPECT studies. Chelate agents of the ^99mTc with thermodynamic stability constants over 16 may be employed in the nearest future as important source for the development of paramagnetic contrast agents binding Mn.

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Abstract:

The preclinical evaluation of the 0,5 M solution of the manganese(II)-DTPA [Mn(II)-DTPA] complex (mangapentetate) has been carried out in order to test the ability of Mangenese to be employed as substiute of potentially toxic Gadolinium in paramagnetic contrast agents for the MRI clinical routines. The toxicologic tests of the Mn(II)-DTPAwere carried out in mice, rats and rabbits. Saline phantoms served for calculation of the R1 -relaxivity of the Mn(II)-DTPA, in comparison to the Gd(III)-DTPA (Magnevist). Normal healthy rabbits (n = 12), healthy dogs (n = 5) and dogs with tumors (n = 5) served for quantification of imaging abilities of the Mn(II)-DTPA in vivo in animals. The LD50 in rats was over 10 ml/kg, essentially close to that one of Gd(III)-DTPA. The increase in intensity oftheTI-weighted images induced by addition of the Mn(II)-DTPA in phantom tests did not differ significantly from the values obtained with gadopentetate. Mn(II)-DTPA delivered prominent enhancement of normal kidneys in healthy rabbits as well as chest tumors in dogs. We conclude the mangapentetate can be employed as paramagnetic contrast agent in routine MRI studies and is worth clinical testing. 

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