Imaging cell death with radiolabeled annexin V in an experimental model of rheumatoid arthritis.

Rheumatoid arthritis is associated with chronic synovial inflammation due to the abnormal accumulation of macrophages and autoreactive T lymphocytes in joints. The autoreactive cells cause an inflammatory proapoptotic response to self-antigens resulting in eventual bone, cartilage, and soft-tissue loss and destruction. The goal of our study was to determine the timing and intensity of apoptosis in joints using 99mTc-labeled annexin V, an in vivo marker of apoptosis, in a murine model of immune arthritis. METHODS: We used 99mTc-annexin V and autoradiography to study the extent and severity of apoptosis in the front and rear paws of DBA/1 mice with type II collagen-induced rheumatoid arthritis. RESULTS: Compared with control values (n = 10), there was a significant (P < 0.002) nearly 3-fold increase in uptake of 99mTc-annexin V in the front foot pads, rear toes, rear foot pads, and heels at the time of maximal extremity swelling as determined by serial caliper measurements at 4 wk after inoculation with type II bovine collagen (n = 9). The front toes had a 5- to 6-fold increase in uptake compared with control values (P < 0.001). Histologic analysis revealed only scattered rare lymphocytes in the periarticular soft tissues, without joint destruction. Dual autoradiography with 125I-bovine serum albumin as a control showed that 99mTc-annexin V localization was specific. Treatment with methylprednisolone for 1 wk (n = 8) at 4 wk after immunization with type II collagen decreased 99mTc-annexin V uptake by 3- to 6-fold compared with control values (P < 0.002). CONCLUSION: 99mTc-annexin V can detect collagen-induced immune arthritis and its response to steroid therapy before joint destruction.     

放射性核素标记annexin V凋亡显像在肿瘤研究中的进展

肿瘤细胞凋亡过低是肿瘤形成的重要原因之一,诱导肿瘤细胞凋亡也成了目前抗肿瘤治疗的研究方向。用放射性核素标记的annexin V对细胞凋亡后暴露在细胞膜表面的体内PS(膦脂酰丝氨酸)进行体内显像,可检测早期细胞凋亡。这种体内凋亡显像方法可以监测抗肿瘤治疗的疗效、评估患者的预后,甚至可以指导肿瘤治疗方法的选择,提高治疗的质量。     

Detection of focal hypoxic-ischemic injury and neuronal stress in a rodent model of unilateral MCA occlusion/reperfusion using radiolabeled annexin V

In this study we wished to determine whether technetium-99m annexin V, an in vivo marker of cellular injury and death, could be used to noninvasively monitor neuronal injury following focal middle cerebral artery (MCA) occlusion/reperfusion injury. Sixteen adult male Sprague-Dawley rats (along with four controls) underwent left (unilateral) MCA intraluminal beaded thread occlusion for 2 h followed by reperfusion. One hour following tail vein injection of 5–10 mCi of ^99mTc-annexin V, animals underwent either single-photon emission computerized tomography (SPECT) or autoradiography followed by immunohistochemical analyses. There was abnormal, bilateral, multifocal uptake of ^99mTc-annexin V in each cerebral hemisphere as seen by both SPECT and autoradiography at 4 h and 1, 3, and 7 days after initiation of occlusion. The average maximal annexin V uptake at 4 h was 310%±85% and 365%±151% above control values (P<0.006) within the right and left hemispheres, respectively, peaking on day 3 with values of 925%±734% and 1,194%±643% (P<0.03) that decreased by day 7 to 489%±233% and 785%±225% (P<0.01). Total lesional volume of the left hemisphere was 226%, 261%, and 451% (P<0.03) larger than the right at 4, 24, and 72 h after injury, respectively. Annexin V localized to the cytoplasm of injured neurons ipsilateral to the site of injury as well as to otherwise normal-appearing neurons of the contralateral hemisphere as confirmed by dual fluorescent microscopy. It is concluded that there is abnormal bilateral, multifocal annexin V uptake, greater on the left than on the right side, within 4 h of unilateral left MCA ischemic injury and that the uptake peaks at 3 days and decreases by 7 days after injury. This pattern suggests that neuronal stress may play a role in the response of the brain to focal injury and be responsible for annexin V uptake outside the region of ischemic insult.Carina Mari and Murat Karabiyikoglu contributed equally to the work presented here.     

Improved detection of cell death in vivo with annexin V radiolabeled by site-specific methods.

Labeled annexin V is widely used to detect cell death in vitro and in vivo. Nearly all studies have been done with annexin V derivatized via amine-directed bifunctional agents; it was thought that these molecules retained full bioactivity compared with unmodified protein. We now show that this assumption is incorrect by measuring the affinity of annexin V for cells in vitro by quantitative calcium titration under conditions of low membrane occupancy. METHODS: Annexin V was modified with 4 different amine-directed agents: the N-hydroxysuccinimide esters of hydrazinonicotinic acid, mercaptoacetyltriglycine, and biotin; and with fluorescein isothiocyanate. RESULTS: In all cases, the membrane-binding affinity was decreased by derivatization, even at very low average stoichiometries. A statistical model based on the Poisson distribution accurately predicted the observed heterogeneity of derivatization as a function of average derivatization stoichiometry. This model also showed that multiply derivatized forms, which are the ones most likely to have compromised bioactivity, contributed disproportionately to the binding and imaging signals. The in vitro binding assay correctly predicted in vivo uptake in a mouse liver model of apoptosis for all proteins tested. The annexin V-128 protein, labeled at a single specific site at the N terminus, showed twice as much apoptosis-specific liver uptake as did all forms of annexin V derivatized randomly via amino groups. CONCLUSION: The membrane-binding activity of annexin V is much more sensitive to amine-directed chemical modification than previously realized. New annexin V molecules labeled by site-specific methods will greatly improve sensitivity for detecting cell death in vivo.     

建立犬脑缺血模型的方法研究

 目的 探索一种经济、实用的建立犬局灶脑缺血模型的技术方法.方法 选择内栓子介入栓塞法和颞部微创手术法进行比较研究,采用DSA检测梗阻结果,MRI扫描结果计算梗死体积及术后14 d内每天的神经功能评分.结果 颞部微创手术法较内栓子介入栓塞法,犬存活时间长,试验成本低,可控性好,能更好地模拟临床.结论 在目前技术条件下,颞部微创手术法是一种更经济、实用的建立犬脑缺血模型的技术方法.     

arcaine 对大鼠局灶性脑缺血损伤的神经保护作用

目的 观察N-甲基-D-天冬氨酸(NMDA)受体/通道复合物多胺位点拮抗剂arcaine对脑缺血损伤的神经保护作用.方法 将45只Wistar大鼠随机分为对照组、缺血模型组、术前24h组、术前1h组及术后1h组.后4组大鼠均采用线栓法阻断大脑中动脉制作急性脑梗死模型.缺血模型组在造模成功后1h给予生理盐水(0.4ml/kg),术前24h组、术前1h组和术后1h组分别在术前24、1h和术后1h给予3mg/kg areaine.检测大鼠神经功能行为、脑梗死体积,并观察光镜及电镜下脑组织损伤情况.结果 神经功能评分显示,术前24h组、术前1h组和术后1h组大鼠神经功能行为评分(1.25±0.46、1.33±0.50、1.40±0.58分)与缺血模型组(2.63±0.52分)相比有显著差异(P<0.05),且术后给药对神经运动功能障碍的改善效果较术前给药效果差(P<0.05).术前24h、术前1h组和术后1h组大鼠脑梗死体积百分比(分别为5.72%±2.91%、26.36%±5.30%、36.35%±6.66%)较缺血模型组(51.10%±3.86%)明显减少(P<0.05);术后1h组大鼠脑梗死体积百分比较术前24、1h组增加(P<0.05).除对照组外,各组光镜下病理分级结果 差异无统计学意义.电镜下观察各组大鼠皮层及海马神经元均有不同程度的变性坏死,其中缺血模型组病理损害最为严重.结论 arcaine能够显著减少脑梗死的体积、减轻梗死所致的神经功能损伤,且预防给药效果更佳,但是arcaine对缺血所致神经元超微结构的损伤无明显逆转作用.     

Radiolabeled annexin V imaging: diagnosis of allograft rejection in an experimental rodent model of liver transplantation

PURPOSE: To assess the value of imaging rejection-induced apoptosis with technetium 99m and annexin V, a human protein-based radiopharmaceutical used in the diagnosis of acute rejection of a liver transplant, in a well-characterized rodent model of orthotopic liver transplantation. MATERIALS AND METHODS: 99mTc-radiolabeled annexin V was intravenously administered to six allografted (immunologically mismatched) and five isografted (immunologically matched) recipient rats on days 2, 4, and 7 after orthotopic liver transplantation. Animals were imaged 1 hour after injection of 0.2-2.0 mCi (8.0-74.0 MBq) of radiolabeled annexin V by use of clinical nuclear scintigraphic equipment. RESULTS: All animals in the allografted group demonstrated marked increases of 55% and 97% above the activity in the isografted group in hepatic uptake of annexin V on days 4 and 7, respectively. Severe acute rejection was histologically detected in all allografted livers on day 7. There was no histologic evidence of acute rejection in isografted animals. Dynamic hepatobiliary imaging with 99mTc and mebrofenin, an iminodiacetic acid derivative, demonstrated no correlation with the presence or absence of acute rejection or with annexin V uptake. CONCLUSION: Noninvasive imaging with radiolabeled annexin V is more sensitive and specific than imaging with 99mTc-mebrofenin in the diagnosis of acute rejection of a liver transplant.     

Detection of cardiomyocyte death in a rat model of ischemia and reperfusion using 99mTc-labeled annexin V.

There is increasing evidence that cell death after myocardial ischemia and reperfusion may begin as apoptosis rather than necrosis. To determine the time course, location, and extent of this process, we studied groups of rats after a 20-min interval of coronary occlusion and reperfusion. METHODS: After thoracotomy, the left coronary artery was occluded for 20 min. After release and before study, groups of animals were allowed to recover for various intervals: 0.5 h (n = 6), 1.5 h (n = 7), 6 h (n = 7), 1 d (n = 8), 3 d (n = 8), or 2 wk (n = 5). At the time of study, the rats were injected with 99mTc-annexin V (80-150 MBq). One hour later, to verify the area at risk, 201Tl (0.74 MBq) was injected intravenously just after the left coronary artery reocclusion and the rats were sacrificed 1 min later. Dual-tracer autoradiography was performed to assess 99mTc-annexin V uptake and the area at risk. RESULTS: Extensive 99mTc-annexin V uptake was observed in the mid myocardium after 0.5-1.5 h of reperfusion. The area of annexin uptake had expanded in the subendocardial and subepicardial layers at 6 h after reperfusion and then gradually lessened over 3 d. At 0.5 and 1.5 h of reperfusion, 99mTc-annexin V uptake ratios were 7.36 +/- 2.95 and 6.34 +/- 2.24 (mean +/- SD), respectively. The uptake ratios gradually decreased at 6 h, 1 d, 3 d, and 2 wk after reperfusion (4.65 +/- 1.93, 3.27 +/- 0.92 [P < 0.01 vs. 0.5 h], 1.84 +/- 0.55 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], and 1.65 +/- 0.31 [P < 0.001 vs. 0.5 h, P < 0.005 vs. 1.5 h], respectively). CONCLUSION: These data indicate that annexin binding commences soon after ischemia and reperfusion in the mid myocardium within the area at risk and expands to include the subendocardial and subepicardial layers at 6 h after reperfusion, followed by gradual reduction of activity over 3 d.     

Apparent diffusion coefficient mapping of experimental focal cerebral ischemia using diffusion-weighted echo-planar imaging

Diffusion-weighted, echo-planar imaging (EPI) was used to map regional changes In the apparent diffusion coefficient (ADC) during experimental focal ischemia in the rat brain following permanent middle cerebral arterial occlusion (MCAO). Sixteen 64 × 64 diffusion-weighted EPIs were acquired in 32 s with successively increasing amplitudes of the diffusion-sensitive gradient pulses. A linear least-squares regression algorithm was used to fit 15 of the 16 two-dimensional matrices, on a pixel-by-pixel basis, to solve for the slope from which the ADC value was calculated. The correlation coefficient of the fit, R² was used to filter the final ADC maps, and the ADCs were then scaled appropriately to be displayed in a 256 gray level format. Ranges (bins) of 0.05 × 10⁻³ mm²/s were then grouped and color coded to qualify and quantify the evolution of ischemia in the MCA territory. The percentage of area in the ischemic and contralateral hemispheres in seven ADC bins were calculated at 30, 60, and 120 min after MCAO for 10 animals and demonstrated a significant increase in ADC bins below 0.45 × 10⁻³ mm²/s and a decrease in bins above 0.50 × 10⁻³ mm²/s over the. The postmortem infarct area, as measured by TTC staining, was highly correlated with the portion of the ischemic hemisphere falling below ADC values of 0.55 × 10⁻³ mm²/s at 2 h after stroke onset. These studies suggest that focally ischemic brain tissue can be quantitatively subdivided according to ADC values and that ADC values below 0.55 × 10⁻³ mm²/s 2 h following ischemia highly predict infarction in a rat permanent occlusion stroke model.     

Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V

Monocytes/macrophages (MJs), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). MJs promote the resolution of inflammation through the induction of apoptosis and phagocytosis of senescent (spent) and bystander (superfluous) granulocytes. We wished to determine whether MCP-1, which selectively binds to MJs, could be used to image subacute and chronic inflammation. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12-week-old male Sprague-Dawley rats by deep intramuscular injection of turpentine into the right thigh. Groups of four to six animals were then imaged 1 h after tail vein injection of 37-148 MBq (1-4 mCi) of ^99mTc-labeled MCP-1 or annexin V 1-14 days after turpentine treatment. Image analysis showed significantly greater activity of both MCP-1 and annexin V in inflamed thighs than in control thighs (165%-290% and 188%-313%, respectively; P<0.01) on days 1-5 after turpentine injection. Dual autoradiography in animals co-injected with iodine-125 labeled bovine serum albumin on days 1 and 4 showed specific location of MCP-1 to infiltrating MJs while annexin V localized to focal zones of apoptosis within granulocytic infiltrates adjacent to abscess cavities. Scintillation well counting on day 5 demonstrated significantly higher (P<0.005) ratios of abscess to control thigh specific activities for MCP-1 (5.83DŽ.17) and annexin V (9.24DŽ.8) as compared to ¹²⁵I-labeled bovine serum albumin (3.11ǂ.65). No significant increases in uptake were noted at imaging or ex vivo analyses on days 13 and 14, when lesions were predominately fibrotic. It is concluded that ^99mTc-labeled MCP-1 and ^99mTc-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of MJs and the incidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.     

Imaging macrophages and the apoptosis of granulocytes in a rodent model of subacute and chronic abscesses with radiolabeled monocyte chemotactic peptide-1 and annexin V

Monocytes/macrophages (Mphis), the predominant cell types in subacute and chronic inflammation, are attracted to and activated by monocyte chemotactic peptide-1 (MCP-1). Mphis promote the resolution of inflammation through the induction of apoptosis and phagocytosis of senescent (spent) and bystander (superfluous) granulocytes. We wished to determine whether MCP-1, which selectively binds to Mphis, could be used to image subacute and chronic inflammation. We also sought to image granulocyte apoptosis within these lesions with technetium-99m labeled annexin V, a marker of apoptotic cells. Sterile inflammation was induced in 45 12-week-old male Sprague-Dawley rats by deep intramuscular injection of turpentine into the right thigh. Groups of four to six animals were then imaged 1 h after tail vein injection of 37-148 MBq (1-4 mCi) of 99mTc-labeled MCP-1 or annexin V 1-14 days after turpentine treatment. Image analysis showed significantly greater activity of both MCP-1 and annexin V in inflamed thighs than in control thighs (165%-290% and 188%-313%, respectively; P<0.01) on days 1-5 after turpentine injection. Dual autoradiography in animals co-injected with iodine-125 labeled bovine serum albumin on days 1 and 4 showed specific location of MCP-1 to infiltrating Mphis while annexin V localized to focal zones of apoptosis within granulocytic infiltrates adjacent to abscess cavities. Scintillation well counting on day 5 demonstrated significantly higher (P<0.005) ratios of abscess to control thigh specific activities for MCP-1 (5.83+/-2.17) and annexin V (9.24 +/- 2.8) as compared to 125I-labeled bovine serum albumin (3.11 +/- 0.65). No significant increases in uptake were noted at imaging or ex vivo analyses on days 13 and 14, when lesions were predominately fibrotic. It is concluded that 99mTc-labeled MCP-1 and 99mTc-labeled annexin V both localize in zones of subacute inflammation, reflecting the density of Mphis and the incidence of apoptotic granulocytes, respectively. These agents may be useful in the characterization of subacute inflammation.     

甾体皂苷化合物对局灶性脑缺血大鼠的保护作用

目的：研究甾体皂苷化合物(化合物9714)对局灶性脑缺血大鼠的影响。方法：采用FeCl3局部损伤血管，诱发血栓形成，造成局灶性脑缺血模型，观察化合物9714对模型大鼠神经症状、脑梗塞范围、脑水肿以及皮质血管脑血流量的影响。结果：化合物9714 20，40mg／kg组能明显减轻模型大鼠的神经症状及脑梗塞范围，增加模型大鼠的脑血流量；化合物9714 40mg／kg组能明显改善模型大鼠的患侧脑水肿程度，延长脑血流量下降50％所需时间。结论：化合物9714对血栓所致局灶性脑缺血性损伤具有明显的修复作用。     

Noninvasive monitoring the biology of atherosclerotic plaque development with radiolabeled annexin V and matrix metalloproteinase inhibitor in spontaneous atherosclerotic mice

Objectives  

To compare the ability of ^99mTc-labeled broad-based matrix metalloproteinase inhibitor (RP805) (MPI) and ^99mTc-annexin V to identify more advanced atherosclerotic disease in apolipoprotein E-null (apoE^−/−) mice.     

急性血栓性大脑中动脉栓塞脑缺血模型的建立

目的评价急性血栓性大鼠大脑中动脉栓塞(MCAO)脑缺血造模的可行性,旨在提高模型的可重复性和可控制性。方法健康雄性成年SD大鼠60只,体重300～450g,随机分为3组:大栓子组(栓子长1.2～1.5mm,15只)、中等栓子组(0.8～1.0mm,30只)和小栓子组(0.5～0.6mm,15只)。取同系大鼠的股动脉血0.6ml与0.15ml凝血酶溶液混匀后,注入微导管内制备成线样血栓。将切好的栓子经大鼠左侧颈内动脉注入,建立MCAO模型。使用GESigna1.5T超导成像仪,3英寸环形表面线圈行大鼠脑MRI检查,并将检查结果与病理结果对照。结果小栓子组15只,9只发现脑梗死灶(60%),中等栓子组和大栓子组所有大鼠均出现脑梗死灶,小栓子组与另2组比较差异有统计学意义(P<0.05)。中等栓子组脑梗死灶均位于同侧大脑半球,局限于左侧顶叶皮质、皮层下及基底节的占93.3%(28/30)。小栓子组9只,在24h或死亡时的平均脑梗死体积占同侧大脑半球的(14.41±8.72)%,中等栓子组30只占(48.29±18.57)%,大栓子组15只占(73.68±18.29)%。3组之间脑梗死体积比较差异有统计学意义(F=33.171,P<0.01)。小栓子组9只,平均生存时间(301.1±23.02)h;中等栓子组30只,平均生存时间(277.43±20.27)h;大栓子组15只,平均生存时间(59.93±25.03)h。大栓子组与另2组之间生存时间比较差异有统计学意义(F=24.676,P<0.01),而中等栓子组的生存时间与小栓子组比较差异无统计学意义(P>0.05)。中等栓子组脑梗死区相对脑血流容量(rCBV)在3～18h内比较差异无统计学意义(F=1.578,P>0.05)。结论经过改良后,中等栓子建立的大鼠MCAO模型脑梗死体积适中、存活率高、脑梗死部位恒定而rCBV持续降低,具有良好的可重复性和可控性。     

Biodistribution and kinetics of radiolabeled proteins in rats with focal infection.

The purpose of this study was to evaluate the role of both protein and radionuclide in the accumulation of 111In-labeled human immunoglobulin G (IgG) in infectious foci. In rats with a calf muscle infection, biodistribution was determined 2, 6, 24, and 48 hr after injection of a radiopharmaceutical. For IgG, human serum albumin (HSA) and human immunoglobulin A (IgA), all labeled with 111In, target-to-background (T/B) ratios were similar throughout the study. However, absolute abscess uptake of 111In-IgA was significantly lower. For IgG labeled with 111In, 123I, or 99mTc, similar T/B ratios were found up to 24 hr. After 48 hr, the T/B ratio of 111In-IgG was significantly higher than the T/B ratio of 123I-IgG. The absolute abscess uptake of 111In-IgG was higher than that of 99mTc-IgG at 24 hr and 123I-IgG at 48 hr. In conclusion, the radionuclide appears to be of major importance in the accumulation of radiolabeled proteins in infectious foci. Protein mainly influences blood clearance and distribution in organs. The Fc-gamma receptor is not crucial for accumulation in infectious foci.     

The stability of proton T2 effects of oxygen-17 water in experimental cerebral ischemia.

The gerbil model of unilateral cerebral ischemia has been used to test the temporal and spatial stability of the MRI T2 effects of oxygen-17 water. Following unilateral carotid ligation, symptomatic animals were given a single large intraperitoneal injection of H2(17)O and the distribution and stability of the brain T2 effects were followed with a spin-echo sequence. In contrast to the ischemic areas, the perfused tissue shows a marked and prolonged loss in intensity with little evidence of diffusion of the T2 effect of 17O into the ischemic tissue.     

Neuroprotective effects of an immunosuppressant agent on diffusion/perfusion mismatch in transient focal ischemia.

The immunosuppressant FK506 (tacrolimus) exerts potent neuroprotection following focal ischemia in animals; however, the separate effects of FK506 on the ischemic core and penumbra have not been reported. The ischemic penumbra is clinically defined as the difference between a large abnormal area on perfusion-weighted imaging (PWI) and a smaller lesion on diffusion-weighted imaging (DWI). The goal of this study was to determine the effect of FK506 on DWI/PWI match and mismatch areas in transient focal ischemia in rats. Twelve rats were subjected to 1 hr of transient middle cerebral artery (MCA) occlusion, and given an intravenous injection of a placebo (N = 6) or 1 mg/kg FK506 (N = 6) immediately before reperfusion. Magnetic resonance imaging (MRI) was performed during MCA occlusion, and 0.5, 1, and 24 hr after reperfusion. FK506 significantly protected the ischemic brain only in the mismatch cortex where the initial apparent diffusion coefficient (ADC) was normal and there was a mild reduction of cerebral blood flow (CBF). This is the first report to describe the protective effects of FK506 on ischemic penumbra, as measured by DWI/PWI mismatch. The findings provide direct evidence for the utility of DWI/PWI mismatch as a guideline for therapeutic intervention with FK506.     

Global and focal cerebral perfusion after aneurysmal subarachnoid hemorrhage in relation with delayed cerebral ischemia

INTRODUCTION: The pathogenesis of delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH) is unclear. We assessed whether DCI relates to focal or global cerebral perfusion on admission and on follow-up imaging. MATERIALS AND METHODS: Twenty-seven SAH patients underwent computed tomography (CT) perfusion (CTP) on admission and at clinical deterioration or 1 week after admission in clinically stable patients. We compared global and focal (least perfused territory) perfusion in patients with DCI (n = 12), clinically stable patients (n = 7), and patients with non-DCI-related deterioration (n = 8). RESULTS: Global cerebral blood flow (CBF) increased on follow-up: 29% (95% confidence interval (CI) 15% to 43%) in patients with DCI, 12% (95%CI -1% to 25%) in stable patients, and 20% (95%CI 4% to 36%) in patients with non-DCI-related deterioration. Focal CBF decreased in patients with DCI, (-23%; 95%CI -58% to 12%) but increased in patients with non-DCI-related deterioration (23%; 95%CI -26% to 55%) and stable patients (7%; 95%CI -30% to 45%).On follow-up, global CBF was lower in patients with DCI (70.0 ml per 100 g/min) than in clinically stable patients (81.6; difference 11.6; 95%CI 0.8 to 22.5 ml per 100 g/min) but comparable to patients with non-DCI-related deterioration (67.6; difference -2.4; 95%CI -11.9 to 7.2 ml per 100 g/min). Focal CBF was lower in patients with DCI (30.7) than in clinically stable patients (53.6; difference 22.9; 95%CI 5.1 to 40.6 ml per 100 g/min) and patients with non-DCI-related deterioration (46.6; difference 15.9; 95%CI -2.6 to 28.4 ml per 100 g/min) CONCLUSION: Our results suggest that DCI is more likely a focal than a global process.     

Analysis of the evolution of focal cerebral ischemia in the rat using the eigenimage filter.

The eigenimage filter was used to evaluate the results of a MRI study of cerebral ischemia in a rat model. This linear filter segments a desired feature in an image sequence from other features which may interfere with its observation. The animals were imaged temporally, after occlusion of the middle cerebral artery, to investigate the evolution of the ischemic process. The temporal evolution of ischemia was evaluated by analysis of the "eigenimages," calculated T2 and T1 map images, and images for the angles between signature vectors defined in the eigenimage technique. The eigenimages and angle map images demonstrated an improved visibility of the lesion at all time points, as compared to the original images and T2 and T1 map images. The eigenimages also demonstrated signal intensity changes within the area of ischemia. These changes are speculated to be related to variations in local cerebral blood flow resulting in varying degrees of tissue damage. The eigenimage intensities and the angles between signature vectors demonstrated time-related changes similar to the T2 and T1 values. Since the eigenimage filter and angle calculations are not dependent upon physical models (like T2 and T1), and the errors associated with these models, they may be preferable as methods for tissue characterization.