Non-enhanced magnetic resonance imaging of unruptured intracranial aneurysms at 7 Tesla: Comparison with digital subtraction angiography.

PURPOSE: To prospectively evaluate non-contrast-enhanced 7-Tesla (T) MRA for delineation of unruptured intracranial aneurysms (UIAs) in comparison with DSA. MATERIAL AND METHODS: Forty patients with single or multiple UIAs were enrolled in this IRB-approved trial. Sequences acquired at 7 T were TOF MRA and non-contrast-enhanced MPRAGE. All patients additionally underwent 3D rotational DSA. Two neuroradiologists individually analysed the following aneurysm and image features on a five-point scale in 2D and 3D image reconstructions: delineation of parent vessel, dome and neck; overall image quality; presence of artefacts. Interobserver accordance was assessed by the kappa coefficient. RESULTS: A total of 64 UIAs were detected in DSA and in all 2D and 3D MRA image reconstructions. Ratings showed comparable results for DSA and 7-T MRA when considering all image reconstructions. Highest ratings for individual image reconstructions were given for 2D MPRAGE and 3D TOF MRA. Interobserver accordance was almost perfect for the majority of ratings. CONCLUSION: This study demonstrates excellent delineation of UIAs using 7-T MRA within a clinical setting comparable to the gold standard, DSA. The combination of 7-T non-enhanced MPRAGE and TOF MRA for assessment of untreated UIAs is a promising clinical application of ultra-high-field MRA. KEY POINTS: • Non-enhanced 7-T MRA allowed excellent delineation of unruptured intracranial aneurysms (UIAs). • Image quality at 7-T was comparable with DSA considering both sequences. • Assessment of UIAs is a promising clinical application of ultra-high-field MRA.

High-Resolution Magnetic Resonance Imaging Can Reliably Detect Orbital Tumor Recurrence after Enucleation in Children with Retinoblastoma.

PURPOSE: Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort. DESIGN: Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation. PARTICIPANTS: A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma. METHODS: High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings. MAIN OUTCOME MEASURES: Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up. RESULTS: Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126). CONCLUSIONS: High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation.

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part II, the cystic gland.

INTRODUCTION: Pineal cysts are a common incidental finding on brain MRI with resulting difficulties in differentiation between normal glands and pineal pathologies. The aim of this study was to assess the size and morphology of the cystic pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. METHODS: In this retrospective multicenter study, 257 MR examinations (232 children, 0-5 years) were evaluated regarding pineal gland size (width, height, planimetric area, maximal cyst(s) size) and morphology. We performed linear regression analysis with 99 % prediction intervals of gland size versus age for the size parameters. Results were compared with a recent meta-analysis of pineoblastoma by de Jong et al. RESULTS: Follow-up was available in 25 children showing stable cystic findings in 48 %, cyst size increase in 36 %, and decrease in 16 %. Linear regression analysis gave 99 % upper prediction bounds of 10.8 mm, 10.9 mm, 7.7 mm and 66.9 mm(2), respectively, for cyst size, width, height, and area. The slopes (size increase per month) of each parameter were 0.030, 0.046, 0.021, and 0.25, respectively. Most of the pineoblastomas showed a size larger than the 99 % upper prediction margin, but with considerable overlap between the groups. CONCLUSION: We presented age-adapted normal values for size and morphology of the cystic pineal gland in children aged 0 to 5 years. Analysis of size is helpful in discriminating normal glands from cystic pineal pathologies such as pineoblastoma. We also presented guidelines for the approach of a solid or cystic pineal gland in hereditary retinoblastoma patients.

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part I, the solid gland.

INTRODUCTION: Differentiation between normal solid (non-cystic) pineal glands and pineal pathologies on brain MRI is difficult. The aim of this study was to assess the size of the solid pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases. METHODS: We retrospectively analyzed the size (width, height, planimetric area) of solid pineal glands in 184 non-retinoblastoma patients (73 female, 111 male) aged 0-5 years on MRI. The effect of age and gender on gland size was evaluated. Linear regression analysis was performed to analyze the relation between size and age. Ninety-nine percent prediction intervals around the mean were added to construct a normal size range per age, with the upper bound of the predictive interval as the parameter of interest as a cutoff for normalcy. RESULTS: There was no significant interaction of gender and age for all the three pineal gland parameters (width, height, and area). Linear regression analysis gave 99 % upper prediction bounds of 7.9, 4.8, and 25.4 mm(2), respectively, for width, height, and area. The slopes (size increase per month) of each parameter were 0.046, 0.023, and 0.202, respectively. Ninety-three percent (95 % CI 66-100 %) of asymptomatic solid pineoblastomas were larger in size than the 99 % upper bound. CONCLUSION: This study establishes norms for solid pineal gland size in non-retinoblastoma children aged 0-5 years. Knowledge of the size of the normal pineal gland is helpful for detection of pineal gland abnormalities, particularly pineoblastoma.

An intact action-perception coupling depends on the integrity of the cerebellum.

It is widely accepted that action and perception in humans functionally interact on multiple levels. Moreover, areas originally suggested to be predominantly motor-related, as the cerebellum, are also involved in action observation. However, as yet, few studies provided unequivocal evidence that the cerebellum is involved in the action perception coupling (APC), specifically in the integration of motor and multisensory information for perception. We addressed this question studying patients with focal cerebellar lesions in a virtual-reality paradigm measuring the effect of action execution on action perception presenting self-generated movements as point lights. We measured the visual sensitivity to the point light stimuli based on signal detection theory. Compared with healthy controls cerebellar patients showed no beneficial influence of action execution on perception indicating deficits in APC. Applying lesion symptom mapping, we identified distinct areas in the dentate nucleus and the lateral cerebellum of both hemispheres that are causally involved in APC. Lesions of the right ventral dentate, the ipsilateral motor representations (lobules V/VI), and most interestingly the contralateral posterior cerebellum (lobule VII) impede the benefits of motor execution on perception. We conclude that the cerebellum establishes time-dependent multisensory representations on different levels, relevant for motor control as well as supporting action perception. Ipsilateral cerebellar motor representations are thought to support the somatosensory state estimate of ongoing movements, whereas the ventral dentate and the contralateral posterior cerebellum likely support sensorimotor integration in the cerebellar-parietal loops. Both the correct somatosensory as well as the multisensory state representations are vital for an intact APC.

High-resolution MRI using orbit surface coils for the evaluation of metastatic risk factors in 143 children with retinoblastoma: Part 2: new vs. old imaging concept.

INTRODUCTION: High-resolution magnetic resonance imaging (MRI) is recommended for the evaluation of metastatic risk factors in children with retinoblastoma according to recent guidelines. The aim of this study was to compare diagnostic accuracy of a new imaging concept with two orbit surface coils to that of an old imaging concept with one orbit surface coil. METHODS: One hundred forty-three patients (148 eyes, 64 girls, 79 boys) underwent high-resolution MRI on 1.5 T scanners using orbit surface coils. The old imaging concept (one orbit surface coil focusing on the (most) effected eye additionally to the standard head coil) was used in 100 patients/103 eye; the new imaging concept (two orbit surface coils (each focusing on one eye) additionally to the standard head coil) in 43 patients/45 eyes. Image analysis was performed by two neuroradiologists in consensus. Histopathology served as gold standard. RESULTS: Detection rate for choroidal invasion was higher for the new compared to that for the old imaging concept (sensitivity/specificity 87.5/94.6 % vs. 57.1/96.1 % for choroidal invasion and 100/97.5 % vs. 58.3/97.7 % for massive choroidal invasion, respectively). Sensitivity and specificity for the detection of postlaminar optic nerve infiltration, peribulbar fat, and scleral invasion were comparable in both imaging concepts; however positive predictive value was higher in the new imaging concept (new vs. old imaging concept: 60 vs. 31.6 % for postlaminar and deep postlaminar optic nerve infiltration, respectively, and 100 vs. 66.7 % for scleral invasion). CONCLUSION: The new imaging concept shows a trend towards improving the accuracy of detecting metastatic risk factors in children with retinoblastoma and is therefore recommended for pretherapeutic imaging and follow-up.

High-resolution MRI using orbit surface coils for the evaluation of metastatic risk factors in 143 children with retinoblastoma: Part 1: MRI vs. histopathology.

INTRODUCTION: A reliable detection of metastatic risk factors is important for children with retinoblastoma to choose the right therapeutic regimen. First studies using high-resolution magnetic resonance imaging (MRI) with orbit surface coils were promising. The aim of this study was therefore to evaluate the ability of high-resolution MRI to detect metastatic and especially advanced metastatic risk factors in a large group of children with retinoblastoma. METHODS: One hundred forty-three consecutive children with retinoblastoma (148 enucleated eyes, 64 girls, 79 boys, mean age 19.7 ± 15.3) who received pretherapeutical high-resolution MRI with orbit surface coils on 1.5 T MR scanner systems between 2007 and 2012 and subsequent primary enucleation within 14 days were included in this retrospective study. Image analysis was performed by two neuroradiologists experienced in ocular imaging in consensus. Histopathology served as gold standard. RESULTS: Sensitivity/specificity for the detection of metastatic risk factors using high-resolution MRI with orbit surface coils were 60 %/88.7 % for postlaminar optic nerve infiltration, 65.5 %/95.6 % for choroidal invasion, 100 %/99.3 % for scleral invasion, and 100 %/100 % for peribulbar fat invasion, respectively. The results increased for the detection of advanced metastatic risk factors, 81.8 %/89.1 % for deep postlaminar optic nerve infiltration, 70.6 %/97.6 % for massive choroidal invasion. CONCLUSIONS: High-resolution MRI is clinically valuable for the detection of metastatic, especially of advanced metastatic risk factors in children with retinoblastoma.

Effects of cerebellar lesions on working memory interacting with motor tasks of different complexities.

We examined the influence of focal cerebellar lesions on working memory (n-back task), gait, and the interaction between working memory and different gait tasks in a dual-task paradigm. The analysis included 17 young patients with chronic focal lesions after cerebellar tumor resection and 17 age-matched controls. Patients have shown mild to moderate ataxia. Lesion sites were examined on the basis of structural magnetic resonance imaging. N-back tasks were executed with different levels of difficulty (n = 1-4) during sitting (baseline), treadmill walking, and treadmill tandem walking (dual-task conditions). Patients exhibited decreased n-back performance particularly at difficult n-back levels and in dual-task conditions. Voxel-based lesion-symptom mapping revealed that decreased baseline n-back performance was associated with lesions of the posterolateral cerebellar hemisphere and the dentate nucleus. By contrast, decreased n-back performance in dual-task conditions was more associated with motor-related areas including dorsal portions of the dentate and the interposed nucleus, suggesting a prioritization of the motor task. During baseline walking, increased gait variability was associated with lesions in medial and intermediate regions, whereas for baseline tandem gait, lesions in the posterolateral hemispheres and the dentate nucleus became important. Posterolateral regions overlapped with regions related to baseline n-back performance. Consistently, we observed increased tandem gait variability with growing n-back difficulty in the dual-task condition. These findings suggest that dual-task effects in cerebellar patients are at least partially caused by a common involvement of posterolateral cerebellar regions in working memory and complex motor tasks.

Evaluation of 100 brain examinations using a 3 Tesla MR-compatible incubator-safety, handling, and image quality.

INTRODUCTION: Several studies have revealed the importance of brain imaging in term and preterm infants. The aim of this retrospective study was to review safety, handling, and image quality of MR brain imaging using a new 3 Tesla MR-compatible incubator. METHODS: Between 02/2011 and 05/2012 100 brain MRIs (84 infants, mean gestational age 32.2 ± 4.7 weeks, mean postmenstrual age at imaging 40.6 ± 3.4 weeks) were performed using a 3 Tesla MR-compatible incubator with dedicated, compatible head coil. Seventeen examinations (13 infants, mean gestational age 35.1 ± 5.4 weeks, mean postmenstrual age at imaging 47.8 ± 7.4 weeks) with a standard head coil served as a control. Image analysis was performed by a neuroradiologist and a pediatric radiologist in consensus. RESULTS: All but two patients with known apnea were transferred to the MR unit and scanned without problems. Handling was easier and faster with the incubator; relevant motion artifacts (5.9 vs. 10.8%) and the need for repetitive sedation (43.0 vs. 86.7%) were reduced. Considering only images not impaired by motion artifacts, image quality (4.8 ± 0.4 vs. 4.3 ± 0.8, p = 0.047) and spatial resolution (4.7 ± 0.4 vs. 4.2 ± 0.6, p = 0.011) of T2-weighted images were scored significantly higher in patients imaged with the incubator. SNR increased significantly (171.6 ± 54.5 vs. 80.5 ± 19.8, p < 0.001) with the use of the incubator. CONCLUSION: Infants can benefit from the use of a 3 Tesla MR-compatible incubator because of its safety, easier, and faster handling (compared to standard imaging) and possibility to obtain high-quality MR images even in unstable patients.

Diagnostic image quality of gadolinium-enhanced T1-weighted MRI with and without fat saturation in children with retinoblastoma.

BACKGROUND: Gadolinium-enhanced T1-weighted MRI without fat saturation has been recommended for assessment of retinoblastoma. OBJECTIVE: The purpose of this study was to compare diagnostic image quality without and with fat saturation following gadolinium administration. MATERIALS AND METHODS: High-resolution gadolinium-enhanced T1-weighted sequences with and without fat saturation performed in children with subsequently histopathologically confirmed retinoblastoma were included. Image analysis (image quality [1 = poor, 2 = moderate, 3 = good], anatomical detail depiction, tumour extension) was performed by two neuroradiologists in consensus. Enhancement was scored and measured. Signal- and contrast-to-noise ratios were calculated. Image-assessed tumour invasiveness was compared to histopathological findings. Paired sample t-test was used for statistical analysis. RESULTS: Thirty-six children (mean age, 19.0 ± 16.8 [SD] months) were included. Image quality and anatomical detail depiction were significantly better without fat saturation (P < 0.001). Tumour enhancement was rated higher with fat saturation (P < 0.001). Fat saturation improved detection of (post-)laminar optic nerve infiltration. Detection of choroidal invasion was improved without fat saturation. Combining both sequences was best in the assessment of tumour extension (sensitivity/specificity for (post-)laminar optic nerve infiltration, 75.0%/100.0%, and for choroidal invasion, 87.5%/85.7%). CONCLUSION: Combined T1-weighted spin-echo imaging with and without fat saturation improved the image quality for assessment of invasiveness of retinoblastoma.

The value of dual-energy CTA for control of surgically clipped aneurysms.

OBJECTIVE: Comparison of image quality in DE-CTA with and without automatic head bone removal (BR) versus CTA with 16-detectors as a tool in postoperative evaluation of patients after neurosurgical clipping. METHODS: In this study 30 aneurysms that had undergone neurosurgical clipping were included: 18 with DE-CTA and 12 with conventional CTA. The images were further processed using the volume rendering technique (VRT) and BR. Two experienced neuroradiologists reviewed the images regarding the severity of artefacts surrounding the clip, visibility of the vessels and remnant necks. The results were compared with DSA images, if performed. RESULTS: Significantly fewer disturbances by artefacts were observed in DE-CTA versus CTA in a 16-row system. Visibility of the surrounding vessels was satisfying in both techniques and there were comparable results with DSA with only one exception. All images produced with 140 kV provided fewer artefacts than those with 80 kV. CONCLUSION: DE-CTA provides better image quality with fewer disturbances by clip artefact, a satisfying evaluation of remnant aneurysm necks and the surrounding vessels. As this method is easily performed and readily accessible with fast image post-processing using BR it provides an opportunity to avoid invasive DSA in the evaluation of suspected aneurysm rests.

Bone metastasis of retinoblastoma five years after primary treatment.

PURPOSE: Histopathological, immunohistochemistry- and molecular pathology-based diagnostics to distinguish metastasis of retinoblastoma from subsequent primary malignancy in patients with heritable retinoblastoma. OBSERVATIONS: An eight year-old girl presented with tibial pain and bone lesion five years after multimodal treatment of bilateral retinoblastoma, initially clinically suspicious of osteomyelitis. Histopathological examination of bone biopsy specimen revealed a highly proliferative small blue round cell tumor mimicking Ewing's sarcoma of bone. Immunohistochemistry confirmed the diagnosis of a distant metastasis of the previous retinoblastoma. Other subsequent primary malignancies presenting as small blue round cell tumors, such as sarcomas or leukemia, were excluded by immunohistochemistry and molecular methods. CONCLUSIONS AND IMPORTANCE: In countries with early diagnosis of retinoblastoma, distant metastases of retinoblastoma are extremely rare, whereas subsequent primary malignancies are common in survivors of heritable retinoblastoma. Immunohistochemistry and molecular pathology are essential components of diagnostic pathway. In retinoblastoma patients, distant metastases including osseous lesions should be included in the differential diagnosis of small blue round cell tumors.

Analysis of intensity normalization for optimal segmentation performance of a fully convolutional neural network.

INTRODUCTION: Convolutional neural networks have begun to surpass classical statistical- and atlas based machine learning techniques in medical image segmentation in recent years, proving to be superior in performance and speed. However, a major challenge that the community faces are mismatch between variability within training and evaluation datasets and therefore a dependency on proper data pre-processing. Intensity normalization is a widely applied technique for reducing the variance of the data for which there are several methods available ranging from uniformity transformation to histogram equalization. The current study analyses the influence of intensity normalization on cerebellum segmentation performance of a convolutional neural network (CNN). METHOD: The study included three population samples with a total number of 218 datasets, all including a T1w MRI data set acquired at 3T and a ground truth segmentation delineating the cerebellum. A 12 layer deep 3D fully convolutional neural network was trained using 150 datasets from one of the population samples. Four different intensity normalization methods were separately applied to pre-process the data, and the CNN was correspondingly trained four times with respect to the different normalization techniques. A quantitative analysis of the segmentation performance, assessed via the Sørensen-Dice similarity coefficient (DSC) of all four CNNs, was performed to investigate the intensity sensitivity of the CNNs. Additionally, the optimal network performance was determined by identifying the best parameter set for intensity normalization. RESULTS: All four normalization methods led to excellent (mean DSC score=0.96) segmentation results when evaluated using known data; however, the segmentation performance differed depending on the applied intensity normalization method when testing with formerly unseen data, in which case the histogram equalization methods outperformed the unit distribution methods. A detailed, systematic analysis of intensity manipulations revealed, that the distribution of input intensities clearly affected the segmentation performance and that for each input dataset a linear intensity modification (shifting and scaling) existed leading to optimal segmentation results. This was further proven by an optimization analysis to find the optimal adjustment for an individual input evaluation sample within each normalization configuration. DISCUSSION: The findings suggest that proper preparation of the evaluation data is more crucial than the exact choice of normalization method to prepare the training data. The histogram equalization methods tested in this study were found to perform this task best, although leaving room for further improvements, as shown by the optimization analysis.

A novel flexible, retrievable endovascular stent system for small-vessel anatomy: preliminary in vivo data.

BACKGROUND AND PURPOSE: This study assessed the in vivo delivery, retrievability, short-term patency, and cellular response to a new flexible endovascular stent system in a rabbit model. The stent is designed for delivery through a microcatheter and is fully retrievable with electrolytic detachment from a delivery wire. METHODS: We successfully deployed nine stents (range of sizes, 2.5-4 mm diameter, 15-35 mm length) in six straight (carotid) and three angled (subclavian) arteries of six Chinchilla Bastard rabbits. Serial imaging was performed by using intravenous digital subtraction angiography (IVDSA), contrast-enhanced MR angiography (CEMRA), time-of-flight MR angiography (TOF), and CT-angiography 3 days and 4 weeks after stent deployment. Subjects were euthenized after 4 weeks (n = 5), and stents were removed for histologic analysis. RESULTS: Stent deployment was feasible in all cases. After initial deployment, all stents could be fully retrieved within the microcatheter. The detachment zone and the distal stent marker were easily visible under fluoroscopy, and final detachment occurred reliably in all cases. We observed no procedural complications. Noninvasive imaging by using IVDSA, MR angiography, and CT angiography was feasible in this stent system and demonstrated all arteries patent and not narrowed at 3 days and 4 weeks, findings that were confirmed by histologic analysis. CONCLUSION: This electrolytically detachable stent is promising as a treatment for intracranial arteries, because it can be delivered through microcatheters small enough for intracranial navigation. It is fully retrievable, thus providing greater control than currently available stents. Noninvasive imaging by using IVDSA, MR angiography, and CT angiography is feasible in this stent system and may be useful for follow-up. Further long-term data are needed.

7 Tesla MPRAGE imaging of the intracranial arterial vasculature: nonenhanced versus contrast-enhanced.

PURPOSE: To intraindividually compare the delineation of intracranial arterial vasculature in nonenhanced versus contrast-enhanced magnetization prepared rapid gradient echo (MPRAGE) imaging at 7 Tesla (T). MATERIALS AND METHODS: Sixteen subjects were examined on a 7 T whole-body magnetic resonance system (Magnetom 7T) equipped with a 32-channel transmit/receive head coil. MPRAGE imaging was performed pre- and postcontrast after the application of 0.1 mmol/kg bodyweight gadobutrol. For qualitative analysis, the delineation of the intracranial arteries, overall image quality, and image impairment were assessed in the nonenhanced and contrast-enhanced datasets using a 5-point scale (5 = excellent to 1 = nondiagnostic). Additionally, contrast ratios (CR) of the middle cerebral artery in correlation to surrounding gray matter in nonenhanced and postcontrast images were obtained. For statistical analysis a Wilcoxon signed-rank test was applied. RESULTS: Nonenhanced MPRAGE imaging offered an excellent delineation of the central vessel segments of the anterior circulation (mean anterior circulation 4.6) and a moderate- to high-quality assessment of the vessels of the posterior circulation (mean posterior circulation 3.9). Vessel delineation was improved in all assessed segments in the contrast-enhanced datasets, except for the cavernous segment of the internal carotid artery. Quantitative analysis revealed a mild, nonsignificant increase in CR mean values of the M1 segment (CRnonenhanced 0.67; CRcontrast-enhanced 0.69). CONCLUSION: Our results demonstrate the high diagnostic value of nonenhanced 7 T MPRAGE imaging for the assessment of the intracranial arterial vasculature, with improved assessment of the peripheral segments because of the application of a contrast agent.

Intrathecal corticoids in permanent focal cerebral ischemia in rats. Part I: a new therapeutic approach in the acute phase.

Intrathecally, triamcinolone acetonide (TCA) was suggested to have neuroprotective efficacy on infarction volume in acute focal cerebral ischemia in rats. In the first dose-finding study, TCA in five different doses or saline was administered into the cisterna magna of 12 rats, each 30 mins after endovascular occlusion of the middle cerebral artery (MCAO). In the second magnet resonance controlled confirmation study, the most neuroprotective dose was compared with controls in each of the 15 rats. Infarction volume was calculated at 24 h by 2.3.5 triphenyl-tetrazolium-chloride staining. Compared with controls (18.2%), infarction volume was significantly reduced using TCA at a dose of 0.012 mg/kg body weight (BW) (13.4%, P=0.04). TCA at doses of 0.03 (17.7%, P=0.84), 0.006 (15.9%, P=0.24), and 0.003 mg/kg BW (14.5%, P=0.11) did not significantly reduce infarction size. TCA 0.3 mg/kg BW resulted in bilateral infarction with increased infarction volume (19.8%, P=0.49). Magnetic resonance imaging confirmed successful MCAO and intrathecal administration. In experiment 2 compared with controls (20.0%), infarction volume was significantly reduced using TCA 0.012 mg/kg (13.4%, P=0.02). Intrathecally, TCA may significantly reduce infarction volume in acute focal cerebral ischemia in rats. Further studies are necessary to define the value of this therapy.