Multiparametric ISODATA analysis of embolic stroke and rt-PA intervention in rat
Introduction
Stroke is a major cause of disability and death [1]. Currently, the only successful acute treatment of stroke is thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) [2], [3]. Diagnostic tools to predict and characterize the efficacy and safety of thrombolysis will greatly improve the management of stroke patients. However, methodologies to evaluate efficacy and risk of thrombolytic treatment have not been fully developed. Since brain tissue undergoes time-dependent heterogeneous histopathological changes after stroke, it is unlikely that a single magnetic resonance imaging (MRI) parameter can characterize the complexity of cerebral tissue at all acute time points [4]. Finding a method to measure ischemic damage after stroke accurately and reproducibly is an important task in diagnostic research.
In the field of MRI, diffusion-, T1- and T2-weighted images (DWI, T1WI, T2WI) can provide complementary information about the status of the cerebral tissue. DWI appears useful for the early detection of stroke [5], [6], [7], [8], [9], [10].
T1, T2 and the apparent diffusion coefficient of water (ADCw) exhibit different temporal profiles in ischemic brain. ADCw declines acutely after onset of ischemia while T2 exhibits a delayed increase compared to ADCw [11], [12]. Conventional T2-weighted MRI provides information on tissue edema [13]. Elevated T2 may identify vasogenic edema and thereby may provide complementary information along with ADCw to distinguish histopathological changes of damaged tissue. By combining information from multiple MRI parameters, it may be possible to determine the histopathological stage in stroke more accurately than using any single MRI parameter.
The multiparametric (multispectral) nature of MRI data for tissue characterization has been reported [14], and various MRI segmentation techniques reviewed [15]. We have recently focused our efforts towards an unsupervised segmentation technique to minimize the need for human interaction and bias. In this method, a vector tissue signature model is used along with a modified version of the Iterative Self-Organizing Data Analysis Technique Algorithm (ISODATA). ISODATA incorporates multiparametric MRI images in an iterative, multistep process that assigns the input data into a set of clusters. ISODATA is an objective unsupervised computer segmentation algorithm [16], [17].
Previous studies using ISODATA have employed image-based ISODATA, and not map-based ISODATA. The map ISODATA is more objective and robust than the image ISODATA in the experiment with surface coil due to the maps are free from the surface correction, which has to be done as pre-processing in image ISODATA. In addition, previous preclinical studies used a mechanical versus embolic occlusion of the MCA. In this study, we applied an unsupervised ISODATA method to incorporate three types of MRI parametric maps or weighted images of embolic stroke rats with and without the treatment of rt-PA at 4 h after the onset of ischemia. For the first time, we tested whether the ISODATA method can identify ischemic lesion in the embolic stroke model in rat with or without rt-PA treatment at 4 h after stroke onset, as a negative control, and compared map versus image ISODATA in the analysis of ischemic lesion volume up to 24 h after stroke.
Section snippets
Materials and methods
All studies were performed in accordance with institutional guidelines for animal research under a protocol approved by the Institutional Animal Care and Use Committee (IACUC).
Results
Physiologic parameters of rats after embolism were maintained within the normal range of values.
Fig. 1 presents a typical set of images from a representative rat obtained at 24 h after stroke onset without rt-PA treatment. The top row contains three MRI images: diffusion- (Fig. 1a), T1- (Fig. 1b) and T2- (Fig. 1c) weighted images. MRI parameter maps of ADCw (Fig. 1d), T1 (Fig. 1e) and T2 (Fig. 1f) are shown in the middle row. The bottom row shows the results of map and image ISODATA (Fig. 1g,h)
Discussion
Our data indicate that map ISODATA provides a more accurate measurement of lesion size at 2, 6 and 24 h after embolic stroke in the rat with or without rt-PA treatment than image ISODATA and select MRI parametric maps of T1, T2 and ADCw. The ISODATA both map and image, provides a time independent (for all time points up to 24 h after the onset of embolic stroke) highly accurate, as measured histologically, and objective analysis method to detect the evolution of ischemic damage.
Most previous
Acknowledgements
This work was supported by NINDS grants PO1 NS23393, RO1 NS38292 and HL64766.
References (52)
- et al.
The temporal evolution of MRI tissue signatures after transient middle cerebral artery occlusion in rat
J. Neurol. Sci
(1997) - et al.
Temporal evolution and spatial distribution of the diffusion constant of water in rat brain after transient middle cerebral artery occlusion
J. Neurol. Sci
(1993) - et al.
Review of MRI segmentation: methods and applications
Magn. Reson. Imaging
(1995) - et al.
A rat model of embolic focal cerebral ischemia
Brain Res
(1997) - et al.
Fast and precise T1 imaging using a TOMROP sequence
Magn. Reson. Imaging
(1990) - et al.
Temporal profile of ischemic tissue damage, neutrophil response, and vascular plugging following permanent and transition (2H) middle cerebral artery occlusion in the rat
J. Neurol. Sci
(1994) Analysis of data from multiclinic trials
Contr. Clin. Trials
(1986)- et al.
The Harvard Cooperative Stroke Registry: a prospective registry
Neurology
(1978) Tissue plasminogen activator for acute ischemic stroke
N. Engl. J. Med
(1995)Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke
Stroke
(1997)
MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders
Radiology
Early detection of regional cerebral ischemia in cats: comparison of diffusion- and T2-weighted MRI and spectroscopy
Magn. Reson. Med
Diffusion-weighted MR imaging and T2-weighted MR imaging in acute cerebral ischemia: comparison and correlation with histopathology
Acta Neurochir., Suppl
Early detection of cerebral ischemia by diffusion-weighted MRI after middle cerebral artery occlusion and reperfusion in rats
J. Neurosurgery
Restricted and anisotropic displacement of water in healthy cat brain and in stroke studied by NMR diffusion imaging
Magn. Reson. Med
Diffusion-weighted imaging studies of cerebral ischemia in gerbils: potential relevance to energy failure
Stroke
Temporal evaluation of ischemic damage in rat brain measured by proton nuclear magnetic resonance imaging
Stroke
Changes of relaxation times (T1, T2) and apparent diffusion coefficient after permanent middle cerebral artery occlusion in the rat: temporal evolution, regional extent, and comparison with histology
Magn. Reson. Med
Multispectral analysis of magnetic resonance images
Radiology
A model for multiparametric MRI tissue characterization in experimental cerebral ischemia with histological validation in rat: Part 1
Stroke
Semi-supervised segmentation of MRI stroke studies
Proc. SPIE Medical Imaging: Image Processing Conference, Newport Beach, CA
Diffusion-, T2-, and perfusion-weighted nuclear magnetic resonance imaging of middle cerebral artery embolic stroke and recombinant tissue plasminogen activator intervention in the rat
J. Cereb. Blood Flow Metab
Rapid NMR imaging of dynamic processes using the FLASH technique
Magn. Reson. Med
Time saving in measurement of NMR and EPR relaxation times
Rev. Sci. Instrum
A comparison of one-shot and recovery methods in T1 imaging
Magn. Reson. Med
Interregional variation of longitudinal relaxation rates in human brain at 3.0 T: relation to estimated iron and water contents
Magn. Reson. Med
Cited by (28)
Mean microvessel segment length and radius after embolic stroke: Comparison of magnetic resonance imaging (MRI) and laser scanning confocal microscopy (LSCM)
2011, Brain ResearchCitation Excerpt :T2-weighted images were taken as reference images for purposes of co-registration, warping, and determination of ischemic lesion size. For this, we considered all lesions on the post-stroke T2 maps with values above the mean ± 2SD of the contralateral measurements (Bosomtwi et al., 2008; Ding et al., 2004). The mean absolute value of T2 in the normal tissue in the contralateral hemisphere is 55.7 + 10.2 ms (mean + 2SD).
Method for tumor recognition with short dynamic PET images: Theory and simulation study
2009, Progress in Natural ScienceDetection of BBB disruption and hemorrhage by Gd-DTPA enhanced MRI after embolic stroke in rat
2006, Brain ResearchCitation Excerpt :It seems difficult to predict and identify all subtypes of HT with MRI using only contrast agent related MRI parameters. Further improvement of prediction and identification of HT may require multiple MRI parameter analysis, such as ISODATA or N-dimension cluster plot analysis (Okada et al., 1994; Ding et al., 2004; Li et al., 2005). Different MRI parameters have different sensitivity in detecting HT.
MRI of combination treatment of embolic stroke in rat with rtPA and atorvastatin
2006, Journal of the Neurological SciencesCharacterization of cerebral tissue by MRI map ISODATA in embolic stroke in rat
2006, Brain ResearchCitation Excerpt :At 48 h after embolism, combination-treated animals showed a significant reduction of lesion area (P < 0.002), mean signature (P < 0.03) and total lesion severity (P < 0.001) compared with the control group. The significant reduction of volume of cerebral infarction using combination rtPA and 7E3 F(ab′)2 treatment at 4 h after embolic stroke compared to rtPA alone and saline groups has been previously reported (Ding et al., 2004, 2005; Zhang et al., 2003). Our data indicate that map ISODATA provides the signatures to characterize the status of cerebral tissue after ischemia which are well correlated with the histological measurements (R ∼ 0.80, P < 0.0001) for all animals treated with saline, rtPA alone and adjuvant treatment with rtPA and 7E3 F(ab′)2 in both kinds of cell counting, i.e., on damaged cells (H&E) at 6 or 24 h after stroke and on normal neurons (MAP2) at 48 h after stroke.