Moyamoyadisease (MMD) occurs in children aged 5 to 9 years and adults aged 45 to 49 years and is one of the leading causes of stroke in children and young adults. Revascularization is the main treatment for MMD, and the rapid development of imaging in recent years has provided a strong basis for the selection of individualized procedures and the determination of prognosis. This article reviews the progress of imaging in the perioperative period of MMD and discusses the value of cerebrovascular imaging and cerebral perfusion imaging in the management of MMD.
1.Cerebrovascular imaging
1.1 Application of cerebrovascular imaging in the perioperative period of MMD
1.1.1 Preoperative application of revascularization
Cerebrovascular imaging can assess the degree of stenosis, smoky vessels and collateral circulation before surgery. Currently, the major vascular imaging methods are digital subtraction angiography (DSA), magnetic resonance angiography (MRA) and computed tomography angiography (CTA), of which DSA is the gold standard for assessing MMD, but it is invasive, risky and expensive, and not easily accepted by patients. CTA is more reliable than MRA for assessing stenosis, but is less able to show smoldering vessels at the skull base than DSA and is radioactive.
Suzuki et al. classified MMD into 6 stages according to the degree of intracranial vascular stenosis or occlusion and compensation of collateral circulation in DSA, which generally reflects the progression of MMD, but DSA performance does not parallel the severity of the disease, so DSA staging at stage II-IV has limitations as an indication for surgery in adult MMD patients. Other studies have applied DSA to score the abundance of collateral circulation to better understand the vascular status of patients with MMD and to provide a basis for preoperative vascular assessment for revascularization.
Houkin et al. used MRA to score the major intracranial vessels in patients with MMD, which were divided into 10 points and 4 grades according to the degree of vascular involvement from mild to severe. the MRA score was significantly consistent with Suzuki staging, and the grading correlated well with Suzuki staging and had high sensitivity and specificity, providing an alternative clinical grading method other than DSA. Some investigators have classified smoldering vessels at the base of the skull into 3 grades, sparse or occluded, small and large, based on the formation of collateral circulation on MRA.
Other investigators have classified the collateral circulation of posterior cerebral artery (PCA) origin into 3 classes: normal, trunk thickening with collateral formation, and trunk stenosis occlusion with collateral reduction; and the collateral circulation of external carotid artery (ECA) origin into 2 classes: normal, trunk thickening with collateral circulation formation.MRA is simple and noninvasive, but the MRA score does not involve smoldering vessels and does not reflect the progression of clinical symptoms. Moreover, the morphology of the arterial wall, distal vascular branches and collateral vessels of the diseased segment are poorer than DSA.
Toshiya et al. used the MRA scoring system created by Houkin as the standard and applied MRA and multi-row spiral computed tomography angiography (MDCTA) to score the degree of stenosis in patients with MMD, respectively, and showed that MRA exaggerated the severity of stenosis for vessel occlusion, whereas MDCTA was more reliable in assessing the degree of stenosis or occlusion, but MDCTA is not ideal for displaying vessels in close proximity to the bone.
The rapidly developing dual-source computed tomography (CT) has two examination techniques for bone artifact removal, namely digital subtraction angiography (Neuro-DSA) and dual-energy CTA (DE-CTA). neuro-DSA requires two scans, which increases the radiation dose and is susceptible to a variety of factors such as patient movement. DE-CTA is efficient, has a low radiation dose, and has the Neuro-DSA has the same quality of intracranial vascular imaging, but the skull base debulking effect needs to be improved. 2009 saw the emergence of energy spectrum CT, which opened up broader clinical applications for energy imaging, where the development of volumetric shuttle scanning technology has increased the scanning range, reduced radiation dose, and 4-dimensional CTA can clearly display the entire Willis ring, while adding a time axis that allows dynamic observe the inflow and outflow of contrast agent, which can simulate the contrast effect of DSA to a certain extent.
1.1.2 Prediction of cerebral hemorrhage events
Reissue of blood is the main cause of poor prognosis and death in MMD. The occurrence of cerebral hemorrhagic events in adult patients with MMD is associated with abnormal compensated vessels, and the increased abundance of smoldering vessels and dilatation of major small intracranial arteries, such as the dilated anterior choroidal artery and posterior communicating artery, shown on cerebral angiography predicts an increased likelihood of cerebral hemorrhagic events.
1.1.3 Assessment of anastomotic vessel diameter and course
Superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis is a common clinical procedure, and the diameter of the STA determines the feasibility of STA-MCA anastomosis; DSA selective external carotid artery angiography can clarify the diameter and direction of the STA, and 3D CTA raw and post-processed images can also show the STA-MCA donor and recipient vessels, providing a basis for the surgical procedure selection. .
1.2 Application of cerebral vascular imaging in revascularization
Indocyanine green angiography can clearly observe the presence or absence of stenosis or occlusion of the vascular anastomosis and the patency of the vessels distal to the anastomosis, and can quantitatively measure the blood flow in the anastomosis with high spatial resolution, which can judge the anastomosis of vessels with a diameter of <5 mm and help reduce the early incidence of vascular anastomosis failure. The disadvantage is that it cannot show the axially traveling vessels and is easily obscured by brain tissue, tampons, blood clots, etc., which does not show the vascular anastomosis.
1.3 Application of cerebral angiography after revascularization
DSA can evaluate the results of direct or indirect revascularization. In addition, techniques such as DSA, CTA or MRA can determine the patency of postoperative vascular anastomosis.
2.Brain perfusion imaging
Although cerebral angiography can effectively assess the vascular condition of MMD patients, the degree of vascular stenosis is not completely consistent with the disease due to factors such as collateral circulation compensation. Cerebral perfusion imaging can reflect the hemodynamic and metabolic conditions from the microcirculatory level, which can quickly and accurately assess the condition and is more in line with clinical reality; therefore, assessing cerebral perfusion has become a new trend in understanding the condition of patients with MMD. Currently, the main perfusion imaging includes positron emission tomography (PET), single photon emission tomography (SPECT), magnetic resonance perfusion imaging (PWI), and CT perfusion imaging (CTP).
2.1 Cerebral hemodynamic characteristics of MMD
Studies have shown that patients with MMD have unique perfusion characteristics, which manifest as decreased local cerebral blood flow (rCBF) in the frontal and temporal lobes and increased rCBF in the occipital lobe, with a significant decrease in rCBF in pediatric MMD patients compared to adults. As Suzuki staging progresses, rCBF gradually decreases and its distribution shows a characteristic predominant posterior circulation perfusion (shift from frontal to occipital lobes). rCBF decreases when the internal carotid artery (ICA) is narrowed or occluded in MMD patients, and is usually compensated by cerebral blood volume (CBV), mean transit time (MTT), and oxygen uptake fraction (OEF). When perfusion pressure decreases, cerebrovascular reactivity (CVR) decreases. patients with MMD have extensively impaired CVR in the ICA blood supply area. impaired CVR often predicts the onset of underlying infarction and can be one of the indications for surgery.
2.2 Application of cerebral perfusion imaging in the perioperative period in patients with MMD
2.2.1 Application of cerebral perfusion imaging in the preoperative period of revascularization
Cerebral perfusion imaging can be used to assess cerebral hemodynamic and metabolic changes before revascularization. rCBF, CBV, OEF, local cerebral glucose metabolic rate (rCMRglu) and local oxygen metabolic rate (rCMRO2) are various perfusion parameters available for PET. When rCBF is balanced with rCMRglu/rCMRO2 at a lower level than the basal value, neuronal function is not restored even with surgical treatment. PET is currently the best method for brain perfusion studies at the in vivo level, but its imaging is complex and expensive, and is mostly used in research centers.
SPECT can not only show hypoperfusion in the frontoparietal-temporal lobe of MMD, but also evaluate cerebrovascular reserve function in combination with vasodilatory tests (e.g. acetazolamide excitation test). Although the spatial resolution of SPECT is poor, it is still widely used in the examination of MMD.
PWI is divided into the arterial proton spin labeling (ASL) method and the dynamic magnetic susceptibility contrast enhancement (DSC) method. The former does not require contrast injection, but only one parameter of CBF can be obtained; the latter requires contrast injection, and four perfusion parameters of CBF, CBV, MTT and time to peak (TTP) can be obtained, with higher temporal and spatial resolution than ASL. Some scholars have used the ASL technique to quantify the onset and termination times of CBF and markers into the vessel to reflect the temporary condition of arterial blood flow, and Tanaka et al. used the comparison of PET and DSC methods to quantify the prolongation of MTT >2s to determine the pre-infarction stage of perfusion abnormalities in patients in stage II, when there must be a decrease in CBV and a decrease in local cerebral perfusion. It has also been shown that the relative regenerative circulation (rR) obtained by the DSC method can be used as an index to assess local cerebral microcirculatory abnormalities. The results of the study showed that MMD patients had rR >35%, TTP time of 6-16s, and rCBV >50%, and the elevation of rR was only seen in the area of prolonged TTP and elevated rCBV. These changes occur only in areas belonging to fine smoky vessels and not in those with thick, well-developed meninges and basal collateral circulation. pWi is radiation-free, quantitative in its determination of perfusion parameters, and provides a noninvasive way of preoperative clinical evaluation.
CTP is divided into two types: intravenous mass injection of iodine-containing contrast agent and inhaled gas (xenon, acetazolamide, etc.). Studies have shown that a decrease in rCBF with a normal or mild decrease in rCBV indicates a mild microcirculatory disturbance; a further decrease in rCBF with a moderate decrease in rCBV is associated with an increased microcirculatory disturbance. When there is no significant difference in CBF in the area supplied by the stenosis compared with the contralateral side, or even when there is hyperperfusion, or when CBF is too low, the bypass surgery results are poor. The CBF parameter at rest is unreliable for predicting impaired CVR, and the percentage of CBF is significantly correlated with quantitative CVR; therefore, the evaluation of CVR in MMD patients needs to be combined with acetazolamide excitation test, and the value of quantitative CVR determination by CTP is significantly correlated with SPECT. However, there are limitations such as radiation, contrast agent side effects.
In addition, cerebral perfusion imaging can predict the risk of postoperative stroke. elevated CBV is the best predictor of postoperative hyperperfusion syndrome. increased OEF is also an independent predictor of stroke risk in patients with MMD. Another study has shown that xenon CT scan combined with acetazolamide excitation test may be useful for stroke risk assessment in children with MMD and may predict good or bad surgical outcome earlier than DSA.
2.2.2 Cerebral perfusion imaging after revascularization
SPECT combined with semi-quantitative imaging can assess the postoperative outcome by measuring the mirror value of perfusion reduction and the magnitude of mirror ratio reduction in the left and right cerebral hemispheres before and after STA-MCA anastomosis. Korean scholar So et al. performed SPECT combined with acetazolamide excitation test in pediatric MMD patients 6 to 12 months after indirect reconstruction and continued follow-up for at least 12 months, showing that patients with reduced cerebral blood flow reserve remained at risk for ischemic stroke and impaired neurological function during follow-up.
Reduction in TTP is a sensitive predictor of normal CBF after STA-MCA. rTTP obtained by PWI differed in absolute values and percentages of preoperative and postoperative changes, with different clinical prognosis. The outcome was better at percentages >2s and >4s, and the absolute value of rTTP change was more statistically significant than the percentage, and the prognosis was very good at (3.10±1.77)s, where the benefit of indirect reconstruction was more definite in children. Significant shortening of TTP in the affected MCA supply area is an indicator of collateral vessel formation between the internal and external carotid arteries. Early evaluation after applying CTP for indirect reconstruction showed that the improvement of perfusion in MMD patients preceded the formation of neovascularization on DSA, and the CTP technique could determine the effect of surgery in advance.
3. Cerebrovascular imaging and cerebral perfusion imaging
3.1 Cerebrovascular and hemodynamic relationships in MMD
It has been shown that the rate of agreement between the site of hypoperfusion and defect in SPECT cerebral perfusion imaging and the corresponding site of cortical ischemic changes due to stenosis or occlusion in MMD patients on DSA is 85.7%. The extent and degree of cortical ischemia due to stenosis of the same vessel on DSA may be related to the degree of stenosis and the formation of collateral circulation. Another study showed that significant prolongation of MTT is one of the characteristics of MMD patients, and the gradation of stenosis and occlusion of anterior and posterior circulation vessels is a significant factor influencing the prolongation of MTT in frontal middle lobe, posterior frontal lobe, occipital lobe and basal ganglia regions in MMD patients, while the abundance of smoky vessels is a significant factor influencing the prolongation of MTT in frontal middle lobe, posterior frontal lobe and occipital lobe regions in MMD patients, and the development of smoky vessels predicts that patients impaired cerebral hemodynamics. A recent study showed that patients with unilateral MMD had a lower incidence of stroke than patients with bilateral MMD, and that rCBF at rest, rCBF after acetazolamide excitation, and CVR were superior to those of patients with bilateral MMD.
3.2 Combined cerebral angiography and cerebral perfusion imaging
The combined application of cerebral angiography and cerebral perfusion imaging can show both morphological changes and reflect physiological function changes, and play an irreplaceable role in the assessment of vascular and perfusion conditions in patients with perioperative MMD. DSA, PET and SPECT can only complete a single examination of vascularity or perfusion, while CT and MR can combine the two. The one-stop examination of PWI has become a new trend in the imaging evaluation of MMD. With the rapid development of imaging, cerebrovascular and cerebral perfusion imaging provides imaging guidance for individualized medical treatment of MMD patients, but the correlation between the degree of cerebral vascular stenosis, perfusion abnormalities and clinical manifestations of MMD patients, and the specific relationship between the area of perfusion abnormalities and the degree of vascular stenosis and the establishment of collateral circulation need to be further investigated.