CTP-Based Tissue Outcome: Promising Tool to Prove the Beneficial Effect of Mechanical Recanalization in Acute Ischemic Stroke.

PURPOSE: To prove the tissue-protecting effect of mechanical recanalization, we assessed the CT perfusion-based tissue outcome ("TO") and correlated this imaging parameter with the 3-month clinical outcome ("CO"). MATERIALS AND METHODS: 159 patients with large intracranial artery occlusions revealing mechanical recanalization were investigated by CCT, CT angiography (CTA) and CT perfusion (CTP) upon admission. For the final infarct volume, native CCT was repeated after 24 h. The "TO" ("percentage mismatch loss" = %ML) was defined as the difference between initial penumbral tissue on CTP and final infarct volume on follow-up CCT. We monitored the three-month modified Rankin Scale (mRS), age, bleeding occurrence, time to recanalization, TICI score and collateralization grade, infarct growth and final infarct volume. Spearman's correlation and nominal regression analysis were used to evaluate the impact of these parameters on mRS.  RESULTS: Significant correlations were found for %ML and mRS (c = 0.48, p < 0.001), for final infarct volume and mRS (c = 0.52, p < 0.001), for TICI score and mRS (c = - 0.35, p < 0.001), for initial infarct core and mRS (c = 0.14, p = 0.039) as well as for age and mRS (c = 0.37, p < 0.001). According to the regression analysis, %ML predicted the classification of mRS correctly in 38.5 % of cases. The subclasses mRS 1 and 6 could be predicted by %ML with 86.4 % and 60.9 % reliability, respectively. No correlations were found for time to recanalization and mRS, for collateralization grade and mRS, and for post-interventional bleeding and mRS.  CONCLUSION: Better than the TICI score, CT-based TO predicts the clinical success of mechanical recanalization, showing that not recanalization, but reperfusion should be regarded as a surrogate parameter for stroke therapy. KEY POINTS: • %ML as well as the final infarct volume can make a direct point about the immediate effect of successful mechanical recanalization.• The clinical outcomes after mechanical recanalization are reliably predicted by %ML, reflecting the benefit of escalation therapy including interventional reopening of parent vessel occlusions.• Not recanalization but rather reperfusion should be regarded as a surrogate parameter for successful stroke therapy.

Reperfusion by combined thrombolysis and mechanical thrombectomy in acute stroke: effect of collateralization, mismatch, and time to and grade of recanalization on clinical and tissue outcome.

BACKGROUND AND PURPOSE: Our research focuses on interventional neuroradiology (stroke treatment including imaging methods) and general neuroimaging with an emphasis on functional MR imaging. Our aim was to determine the efficacy of revascularization (TIMI) of middle cerebral and/or carotid artery occlusion by means of mechanical recanalization techniques and to evaluate the impact of collateralization, mismatch in perfusion CT, time to revascularization, grade of revascularization on tissue, and clinical outcome in patients with acute ischemic stroke. MATERIALS AND METHODS: Thirty-one patients with MCA and/or ICA occlusion were included. Ischemic stroke was diagnosed by NECT, CTA, and volume PCT for grading collateralization and mismatch. Time to recanalization was measured from the onset of stroke to the time point of DSA-proved mechanical recanalization. Tissue outcome was calculated by segmentation of infarct size between pre- and postinterventional CT and percentage mismatch lost. Clinical outcome was determined by the mRS. RESULTS: Twenty-one of 31 patients (61.8%) presented with MCA and 10/31 patients (38.2%), with distal ICA occlusions. Sufficient recanalization (TIMI 2 and 3) was achieved in 23/31 (75%). Clinical evaluation revealed an mRS score of ≤2 in 25.5%. Age (r = 0.439, P = .038) and TIMI (r = 0.544, P = .002) showed the strongest correlation with clinical outcome. Time to recanalization, TIMI score, and mismatch were associated with a good tissue outcome in ANOVA. CONCLUSIONS: Favorable outcome after mechanical recanalization of acute MCA and ICA occlusion depends on time to and grade of recanalization, mismatch, and collateralization. These results indicate that multimodal stroke imaging is helpful to guide therapy decisions and to indicate patients amenable for mechanical recanalization.

Development of chronic hydrocephalus and early cranial CT findings in spontaneous intracerebral/intraventricular hemorrhage.

INTRODUCTION: Since intracerebral hemorrhage (ICH) is frequently associated with intraventricular bleeding (IVH), we sought to detect cranial computed tomography features that would indicate early on in the patient's history the development of chronic hydrocephalus with a permanent need for cerebrospinal fluid (CSF) diversion. METHODS AND MATERIALS: A total of 25 consecutive cases presenting with ICH/IVH was studied retrospectively. Outcome was assessed using the Glasgow Outcome Scale at an average of 8 months subsequently. Diagnosis of ICH/IVH and (acute) hydrocephalus was made by early cranial CT scanning employing a selection of radiological criteria according to the literature including the Evans ratio. All patients then received external ventricular drainage. Chronic hydrocephalus was diagnosed by intraventricular pressure monitoring or by cranial CT follow-up after removal of the external drainage. RESULTS: None of the radiological criteria nor the scores obtained differed between the two groups. However, the ratio of scores for IVH/ICH was higher among the patients who developed a chronic hydrocephalus. All other parameters including volume of ICH and IVH were equally distributed. Overall outcome was poor with a median GOS score of 3. CONCLUSIONS: The ICH/IVH ratio presented here can be interpreted as an individual measure of propensity to impairment of CSF circulation. Further studies on larger populations will be needed to show whether this can be employed as an early diagnostic criterion with respect to chronic hydrocephalus.

Propofol attenuates responses of the auditory cortex to acoustic stimulation in a dose-dependent manner: a FMRI study.

BACKGROUND: Functional magnetic resonance imaging (fMRI) using blood-oxygen-level-dependent (BOLD) contrasts is a common method for studying sensory or cognitive brain functions. The aim of the present study was to assess the effect of the intravenous anaesthetic propofol on auditory-induced brain activation using BOLD contrast fMRI. METHODS: In eight neurosurgical patients, musical stimuli were presented binaurally in a block design. Imaging was performed under five conditions: no propofol (or wakefulness) and propofol plasma target concentrations of 0.5, 1.0, 1.5, and 2.0 microg ml(-1). RESULTS: During wakefulness we found activations in the superior temporal gyrus (STG) corresponding to the primary and secondary auditory cortex as well as in regions of higher functions of auditory information processing. The BOLD response decreased with increasing concentrations of propofol but remained partially preserved in areas of basic auditory processing in the STG during propofol 2.0 microg ml(-1). CONCLUSIONS: Our results suggest a dose-dependent impairment of central processing of auditory information after propofol administration. These results are consistent with electrophysiological findings measuring neuronal activity directly, thus suggesting a dose-dependent impairment of central processing of auditory information after propofol administration. However, propofol did not totally blunt primary cortical responses to acoustic stimulation, indicating that patients may process auditory information under general anaesthesia.

Computed-tomography-guided percutaneous core needle biopsies of suspected malignant lymphomas: impact of biopsy, lesion, and patient parameters on diagnostic yield.

PURPOSE: To investigate the diagnostic yield of core needle biopsy in patients with malignant lymphoma. MATERIAL AND METHODS: Computed-tomography-guided core needle biopsies in patients with malignant lymphoma performed in the period 1996 to 2001 were evaluated retrospectively. A biopsy was considered as "fully diagnostic" if a histological diagnosis, including the histologic subtype in the event of malignant lymphoma, was achieved and the clinical course and CT follow-up of at least 6 months confirmed the biopsy results. A biopsy was regarded as "partly diagnostic" if histological work-up defined malignant lymphoma but not the histological subtype, and if histological diagnosis bore therapeutic relevance. Diagnostic yield was correlated with features such as size of specimen, location and depth of the target lesion, and experience of the investigator. RESULTS: 45 biopsies were performed in 40 patients. With respect to definite histopathological diagnosis, 31 biopsies (68.9%) were diagnostic and 14 (31.1%) non-diagnostic. In 4 cases (8.8%), biopsies yielded partly diagnostic results, since therapy could be scheduled after biopsy without final sub-classification. Statistical analysis of biopsy parameters revealed that sample sizes were significantly larger in the diagnostic group. CONCLUSION: CT-guided biopsy can be considered as an alternative for lymphoma diagnosis and should be the first interventional procedure. The most important parameter for diagnostic success is the size of the specimen.

Which time-to-peak threshold best identifies penumbral flow? A comparison of perfusion-weighted magnetic resonance imaging and positron emission tomography in acute ischemic stroke.

BACKGROUND AND PURPOSE: In acute ischemic stroke, the hypoperfused but viable tissue is the main therapeutic target. In clinical routine, time-to-peak (TTP) maps are frequently used to estimate the hemodynamic compromise and to calculate the mismatch volume. We evaluated the accuracy of TTP maps to identify penumbral flow by comparison with positron emission tomography (PET). METHODS: Magnetic resonance imaging (MRI) and PET were performed in 11 patients with acute ischemic stroke (median 8 hours after stroke onset, 60 minutes between MRI and PET imaging). The volumes defined by increasing TTP thresholds (relative TTP delay of >2, >4, >6, >8, and >10 seconds) were compared with the volume of hypoperfusion (<20 mL/100 g per min) assessed by 15O-water PET. In a volumetric analysis, each threshold's sensitivity, specificity, and predictive values were calculated. RESULTS: The median hypoperfusion volume was 34.5 cm3. Low TTP thresholds included large parts of the hypoperfused but also large parts of normoperfused tissue (median sensitivity/specificity: 93%/60% for TTP >2) and vice versa (50%/91% for TTP >10). TTP >4 seconds best identifies hypoperfusion (84%/77%). The positive predictive values increased with the size of hypoperfusion. CONCLUSIONS: This first comparison of quantitative PET-CBF with TTP maps in acute ischemic human stroke indicates that the TTP threshold is crucial to reliably identify the tissue at risk; TTP >4 seconds best identifies penumbral flow; and TTP maps overestimate the extent of true hemodynamic compromise depending on the size of ischemia. Only if methodological restrictions are kept in mind, relative TTP maps are suitable to estimate the mismatch volume.

Acute demyelination: diagnostic difficulties and the need for brain biopsy.

BACKGROUND: Despite the rapid development in neuro-imaging over the past two decades, ring like contrast-enhancing lesions on CCT or MRI still may pose a diagnostic challenge. The main differential diagnoses of these lesions include metastatic carcinoma, high-grade glioma and brain abscess. Acute demyelination seldom turns out to be the underlying pathology. METHOD: Retrospective analysis was done on six patients with acute demyelination treated at our neurosurgical department between 1990 and 2001. Clinical, radiological, PET, intra-operative and histological findings were evaluated. FINDINGS: In five patients, the diagnosis of acute demyelination was established by histopathological evaluation of stereotactic biopsy specimen, in the sixth patient following microsurgical extirpation of the lesion. Neuropathology revealed demyelination with the presence of myelin-phagocytosing macrophages. In addition, lymphocytic infiltrates were present. Symptoms and signs improved significantly after high-dose steroid therapy. CONCLUSIONS: Despite CNS tissue destruction, necrosis and cyst formation are not usually found in demyelinating disease, being rather more common in young patients with ring-like contrast-enhancing lesions on CCT and MRI. Though an incorrect diagnosis can lead to a potentially fatal therapeutic intervention, histological diagnosis should be made in all cases. Due to minimum morbidity, stereotactic biopsy is the method of choice to obtain representative specimens for histological diagnosis. Open microsurgery of these lesions is not indicated since conservative medical treatment with steroids results in a favourable outcome in most cases.

Reducing the radiation dose during excretory urography: flat-panel silicon x-ray detector versus computed radiography.

OBJECTIVE: The purpose of the study was to examine the possibilities for reducing radiation exposure in uroradiology using digital flat-panel silicon X-ray detector radiography. We compared the subjectively determined image quality of abdominal radiographs and urograms obtained on a digital flat-panel detector radiography system with those obtained on a computed radiography system. SUBJECTS AND METHODS. Fifty patients who had a clinical indication for urography underwent unenhanced abdominal imaging that was alternately performed using flat-panel silicon X-ray detector radiography or computed radiography. For patients who required a second radiograph with contrast medium, the examination modality was changed to avoid exposing the patients to excess radiation. The images obtained on flat-panel X-ray detector radiography were obtained at half the radiation dose of the images obtained on computed radiography (800 speed vs 400 speed). The resulting 50 pairs of images were interpreted by four independent observers who rated the detectability of structures of bone and the efferent urinary tract relevant to diagnosis and compared the image quality. RESULTS: At half the radiation dose, digital flat-panel X-ray detector radiography provided equivalent image quality of the liver and spleen, lumbar vertebrae 2 and 5, pelvis, and psoas margin on abdominal radiographs. The image quality obtained with digital flat-panel X-ray detector radiography of the kidneys, the hollow cavities of the upper efferent urinary tract, and the urinary bladder was judged to be statistically better than those obtained with computed radiography. CONCLUSION: With half the exposure dose of computed radiography, the flat-panel X-ray detector produced urograms with an image quality equivalent to or better than computed radiography.

Trauma to the pontomesencephalic brainstem-a major clue to the prognosis of severe traumatic brain injury.

The objective of this study was to assess the significance of an injury to the pontomesencephalic brainstem in severe traumatic brain injury [Glasgow coma score (GCS) below 8]. Forty victims of severe traumatic brain injury with and with out compounding pathologies almost equally distributed among both groups were studied. The outcome (mean follow-up, 11.3 months) was assessed by means of the Glasgow outcome score (GOS) and of the Disability rating scale (DRS). Injury of the brainstem was detected by electrophysiological investigation (evoked potentials, brainstem reflexes) and magnetic resonance imaging (MRI) carried out early after trauma. Statistical analysis (Wilcoxon signed rank test for matched pairs) revealed a significantly worse initial GCS (median 5 versus 6), GOS (median 3 versus 4), and DRS score (median 6 versus 2) for the group with brainstem lesions than for the group without such lesions. Moreover, there was a significant accumulation of lesions of the corpus callosum, the basal ganglia, and the (para-)hippocampal area detected by MRI in the brainstem lesion group. In addition, the finding of an abnormal cortical component of the median nerve evoked somatosensory potential was significantly more frequent in the patients with brainstem injury. Traumatic brainstem lesions diagnosed by MRI a nd/or electrophysiological investigation are associated with injury to other 'deeply' situated parts ofthe brain. The finding of a brainstem lesion influences to the outcome of patients after severe traumatic brain injury.

Functional magnetic resonance imaging of human pontine auditory pathway.

The purpose of this study is to visualize brainstem auditory pathways by functional magnetic resonance imaging (fMRI). Eighteen healthy volunteers (age 28 to 42 years) with normal hearing function underwent fMRI examination on a 1.5 Tesla imaging system (Philips, Best, The Netherlands) with periodic click stimulation. Blood oxygen level dependent images were obtained using a three-dimensional EPI sequence with shifted echo technique (principles of echo shifting with a train of observations). Control scans without click stimulation were obtained in the identical setting. Cross correlation activation maps were calculated using a postprocessing tool (Philips). They were matched with anatomic slices of identical orientation and thickness. Five of 18 subjects were excluded because of motion artifacts. In 4/13 significant activation was observed at the root entry zone of the ipsilateral acoustic nerve corresponding to the cochlear nuclei. In 11/13 subjects, significant activation was found in the same slice contralaterally close to the floor of the 4th ventricle, corresponding to the expected region of the superior olivary nucleus. Activation of the rostral parts of the auditory pathway (inferior colliculus, medial geniculate body) was not found. In the absence of the stimulus no activation occurred in these structures. It was concluded that activation of the brainstem auditory pathways by click stimuli can be visualized by fMRI.

Age related signal decrease in functional magnetic resonance imaging during motor stimulation in humans.

Right handed healthy volunteers underwent functional magnetic resonance imaging (fMRI) examinations on a 1.5 Tesla MRI-scanner (Gyroscan ACS NT; Philips, Best, NL). Blood oxygen level dependent (BOLD) images were obtained using a three dimensional multi-shot echo planar imaging sequence employing a shifted echo technique (Principles of echo shifting with a train of observations). Finger tapping of the right hand was used as a task for motor stimulation. A total of 86 subjects was included into statistical analysis. Absolute and relative signal differences and cluster sizes of activation for the left motor cortex were obtained. In addition, Z-score, pooled Z-score and cross correlation activation maps were calculated and matched with high resolution anatomic images. A significant decrease with age could be detected for absolute and relative signal intensity differences for the whole group and for the male subgroup. Correlation analysis for the female subgroup also bore negative albeit non-significant correlation coefficients. An age-related decline of BOLD-contrast can be assumed to explain signal decrease. This age-related effect should be considered in clinical fMRI applications.

Quantitative kinetics of [124I]FIAU in cat and man.

UNLABELLED: For the assessment of the efficacy of clinical gene therapy trials, different imaging modalities have been developed that enable a noninvasive assessment of location, magnitude, and duration of transduced gene expression in vivo. These imaging methods rely on a combination of an appropriate marker gene and a radiolabeled or paramagnetic marker substrate that can be detected by PET or MRI. Here, we assess whether the nucleoside analog 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyl-5-iodouracil (FIAU), a specific marker substrate for herpes simplex virus type 1 thymidine kinase (HSV-1-tk) gene expression, penetrates the blood-brain barrier (BBB) as an essential prerequisite for a noninvasive assessment of HSV-1-tk gene expression in gliomas. METHODS: No-carrier-added [(124)I]FIAU was synthesized by reacting the precursor 2'-fluoro-2'-deoxy-1beta-D-arabinofuranosyluracil (FAU) with carrier-free [(124)I]NaI. The course of biodistribution of [(124)I]FIAU was investigated in anesthetized cats (n = 3; organs) and in one patient with a recurrent glioblastoma (plasma and brain) by PET imaging over several hours (cats, 1-22 h) to several days (patient, 1-68 h). FIAU PET was performed in conjunction with multitracer PET imaging (cerebral blood flow and cerebral metabolic rate of O(2) in cats only; cerebral metabolic rate of glucose and [(11)C]methionine in all subjects). A region-of-interest analysis was performed on the basis of coregistered high-resolution MR images. The average radioactivity concentration was determined, decay corrected, and recalculated as percentage injected dose per gram of tissue (%ID/g) or as standardized uptake values (SUVs). RESULTS: The average chemical yield of [(124)I]FIAU synthesis was 54.6% +/- 6.8%. The chemical and radiochemical purities of [(124)I]FIAU were found to be >98% and >95%, respectively. In cats, the kinetic analysis of [(124)I]FIAU-derived radioactivity showed an early peak (1-2 min after injection) in heart and kidneys (0.20 %ID/g; SUV, 4.0) followed by a second peak (10-20 min after injection) in liver and spleen (0.16 %ID/g; SUV, 3.2) with subsequent clearance from tissues and a late peak in the bladder (10-15 h after injection). In the unlesioned cat brain, no substantial [(124)I]FIAU uptake occurred throughout the measurement (<0.02 %ID/g; SUV, <0.4). In the patient, [(124)I]FIAU uptake in normal brain was also very low (<0.0002 %ID/g; SUV, <0.16). In contrast, the recurrent glioblastoma revealed relatively high levels of [(124)I]FIAU-derived radioactivity (5-10 min after injection; 0.001 %ID/g; SUV, 0.8), which cleared slowly over the 68-h imaging period. CONCLUSION: The PET marker substrate FIAU does not penetrate the intact BBB significantly and, hence, is not the marker substrate of choice for the noninvasive localization of HSV-1-tk gene expression in the central nervous system under conditions in which the BBB is likely to be intact. However, substantial levels of [(124)I]FIAU-derived radioactivity may occur within areas of BBB disruption (e.g., glioblastoma), which is an essential prerequisite for imaging clinically relevant levels of HSV-1-tk gene expression in brain tumors after gene therapy by FIAU PET. For this purpose, washout of nonspecific radioactivity should be allowed for several days.

[Precision of MRI-guided needle placement--experimental results]. / Präzision der Lokalisierbarkeit einer Punktionsnadel in der MRT--experimentelle Ergebnisse.

PURPOSE: To estimate the accuracy of the determination of tip position of MR compatible biopsy needles based on signal voids and artifacts in MR guided biopsies. METHOD: In a nylon grid phantom an MR compatible 18G needle (E-Z-EM) was measured in a 1.0 T imager using TSE- and FFE-sequences of 20 s and 40 s duration in 34 different orientations of needle versus B0, frequency and slice selection gradient. 4 radiologists with no experience in the evaluation of signal void artifacts estimated the needle tip positions from needle tip artifacts. The readers determined the needle tip before and after a 15 minute training session based on high resolution images with explanation of size and shape of specific artifacts of biopsy needles in 12 different orthogonal or parallel orientations to B0 and frequency encoding gradient that are possible if the needle lies parallel to the slice, i.e. orthogonal to the slice selection gradient. The values obtained before and after the training session were compared to the real position of the needle tip. RESULTS: Mean distance of actual needle tip and tip position as determined from images was 1.8 +/- 2.3 mm in TSE-versus 2.5 +/- 1.2 mm in FFE-images, with the needle length overestimated. After a 15 minute training session the positioning error decreased significantly to 0.2 +/- 1.8 mm for TSE-sequences and to 1.0 +/- 1.8 mm for FFE-sequences. A higher accuracy of tip localization was obtained with TSE sequences. CONCLUSION: In MR guided biopsies using FFE- and TSE-sequences the needle position can be more accurately determined if the reader is familiar with the 12 orthogonal or parallel positions of the needle with respect to B0 and frequency encoding gradient and the corresponding artifacts.

Functional anatomy of intrinsic alertness: evidence for a fronto-parietal-thalamic-brainstem network in the right hemisphere.

Alertness, the most basic intensity aspect of attention, probably is a prerequisite for the more complex and capacity demanding domains of attention selectivity. Behaviorally, intrinsic alertness represents the internal (cognitive) control of wakefulness and arousal; typical tasks to assess optimal levels of intrinsic alertness are simple reaction time measurements without preceding warning stimuli. Up until now only parts of the cerebral network subserving alertness have been revealed in animal, lesion, and functional imaging studies. Here, in a 15O-butanol PET activation study in 15 right-handed young healthy male volunteers for this basic attention function we found an extended right hemisphere network including frontal (anterior cingulate-dorsolateral cortical)-inferior parietal-thalamic (pulvinar and possibly the reticular nucleus) and brainstem (ponto-mesencephalic tegmentum, possibly involving the locus coeruleus) structures, when subjects waited for and rapidly responded to a centrally presented white dot by pressing a response key with the right-hand thumb.