Spatial and temporal evolution of hemorrhage in the hyperacute phase of experimental spinal cord injury: In vivo magnetic resonance imaging

Bilgen, Mehmet; Abbe, Russell; Liu, Shi Jie; Narayana, Ponnada A.

doi:10.1002/(sici)1522-2594(200004)43:4<594::aid-mrm15>3.0.co;2-1

Cited by 64 publications

(67 citation statements)

References 35 publications

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“…Likewise, prior studies relating neurologic status to MR imaging findings have not accounted for the potential effects of time to MR imaging, despite the fact that animal studies clearly show that early SCI lesions are dynamic. 13,14 Because most patients are imaged early, an understanding of the early evolution of SCI lesions would be important in the initial diagnosis of SCI, both for the accurate determination of functional prognosis and for the performance of clinical research, particularly with regard to studies designed to test novel therapies that use MR imaging findings as selection criteria or as surrogate outcome measures. Animal studies have correlated the histopathology of acute SCI with MR imaging findings.…”

Section: Discussionmentioning

confidence: 90%

“…Consistent with the results of animal studies, 13,14 we did not observe the presence of T2 hyperintense oxyhemoglobin even in the patients imaged most rapidly after injury (n ϭ 4 patients imaged at Ͻ6 hours, the earliest imaged at t ϭ 2.5 hours). Bilgen et al 14 studied animals 9 -400 minutes postinjury and reported that hemorrhage appears hypointense on T2-weighted images, even at the earliest times.…”

Section: Discussionmentioning

confidence: 99%

“…11,12 Work in animals has shown that intramedullary spinal cord hemorrhage and edema are dynamic, whether assessed by histopathology or MR imaging. 13,14 The extent to which cord lesions evolve in patients during the early phase of SCI (ie, the first hours and days postinjury) is unknown; therefore, given similar clinical deficits, it is unclear to what extent variability in lesion size reflects differences in time to imaging after trauma. Similarly, it is not clear whether lesion expansion when observed on a short-interval follow-up MR imaging study is an ominous sign or a usual feature in the natural evolution of SCI.…”

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confidence: 91%

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The Early Evolution of Spinal Cord Lesions on MR Imaging following Traumatic Spinal Cord Injury

Leypold¹,

Flanders²,

Burns³

2008

AJNR Am J Neuroradiol

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

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The Early Evolution of Spinal Cord Lesions on MR Imaging following Traumatic Spinal Cord Injury

Leypold¹,

Flanders²,

Burns³

2008

AJNR Am J Neuroradiol

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“…The room temperature shim power supply (RTS-50; Nalorac, Martinez, CA) was controlled and monitored continuously by a Labview (National Instruments, Austin, TX) based GUI software that was written in-house. Prior to imaging the cord, a phase map-based technique was used to homogenize the magnetic field near the magnet isocenter using a 50-cc water phantom containing 5% NaCl and 0.1 mM MnCl 2 in deionized water (16). This shimming minimized the time interval between the injury and acquisition of the first image on the day of injury.…”

Section: Dce-mri Data Acquisitionmentioning

confidence: 99%

Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies

Bilgen¹,

Abbe²,

Narayana³

2001

Magnetic Resonance in Med

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The progression of experimental spinal cord injury (SCI) was followed with in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and neurobehavioral studies on postinjury days 0, 2, 4, 7, 10, 14, 17, 21, 28, 35, and 42. Gadopentate dimeglumine (Gd) was administered IV and postcontrast, T 1 -weighted, axial images were acquired repetitively for up to 60 min. Images were analyzed to determine the spatial and temporal evolution of the intensity enhancement. A statistical decision mechanism was developed to objectively detect the enhancement. Strong and rapid enhancement was observed at the epicenter of injury, indicating a significant compromise in blood spinal cord barrier. The enhanced regions in each slice were combined to estimate the area and volume of the lesion. On the day of injury, around 85% of the total cord area at the epicenter showed enhancement within the first 15 min of Gd administration. At the same time, the enhanced volumes attained nearly 40% of the total cord volume and extended axially over 8 mm along the cord. The blood-spinal cord barrier (BSCB) maintains a highly regulated homeostatic environment in the spinal cord (SC) tissue. This regulatory function is sustained by various structures, including the capillary endothelial tight junctions. Under normal physiological conditions, BSCB protects the cord tissue by exhibiting selective permeability to the constituents of intravascular fluid (1,2). A traumatic insult to SC disrupts the structural and biochemical integrity of BSCB. The altered tight junctional patency allows vesicular transport of toxic substances from blood plasma to interstitial spaces. This makes the SC tissue environment unfavorable for neuronal survival, and inhibits tissue repair processes and neurologic recovery. By following the changes in BSCB after injury, important information may be gained about the regions of initial SC tissue damage and a time window for effective drug delivery across the barrier. Assessing BSCB in the late phases of the injury may help evaluate the progression of spinal cord injury (SCI) as well as the efficacy of potential therapeutic interventions.Changes in BSCB permeability can be followed experimentally using intravascularly administered tracers (such as plasma proteins, radiolabeled proteins, and small-molecular-weight molecules) that can cross the compromised barrier (3,4). Although these tracer-based techniques provide valuable information about the status of BSCB, they are either fully invasive, necessitating histological analysis of tissue, or less invasive but still requiring intravenous injection of radio-tracers with subsequent blood sampling along with imaging, as in the case of autoradiography. Moreover, active transport mechanisms involved in some of these tracers may introduce a bias in quantifying the BSCB permeability (4).As an alternative to the above techniques, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), with the exogenous paramagnetic contrast agent gadopentetate-dimeglumine (Gd, for short)...

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“…This coil was coupled inductively to an external coil measuring 15 ϫ 30 mm in size. The details of the injury device, coil fabrication, and its implantation in animals are provided elsewhere (7,8). For intravenous delivery of Gd, the left jugular vein was cannulated with a 60-cm-long catheter (PE-50 tube, Clay Adams, NJ).…”

Section: Animals and Scimentioning

confidence: 99%

A pharmacokinetic model for quantitative evaluation of spinal cord injury with dynamic contrast‐enhanced magnetic resonance imaging

Bilgen¹,

Narayana²

2001

Magnetic Resonance in Med

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Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows in vivo measurement of many physiological parameters of clinical interest (1-3). Following intravenous administration, the exogenous paramagnetic contrast agent gadopentetate-dimeglumine (Gd) is distributed throughout the body, except in the central nervous system (CNS) tissue because of the blood-brain barrier (BBB) and the blood-spinal cord barrier (BSCB). In the presence of CNS pathology, the barrier is regionally disrupted; Gd no longer remains intravascular and leaks into the interstitial tissue spaces. Measuring the rate of this leakage facilitates quantitative evaluation of barrier permeability. For example, the BBB in brain tumors or injuries was successfully characterized in vivo using Gd concentration data obtained from DCE-MRI (4). This technique has not yet been applied to evaluate the status of BSCB following traumatic spinal cord injury (SCI) or disease. Quantitative measurements of changes in BSCB permeability in vivo can be used to assess the severity of injury, monitor the evolution of cord pathology, identify the effective time interval for delivering drugs to the cord tissue across the compromised barriers, and observe the endogeneous repair processes (5).In this paper, we report results from in vivo DCE-MRI experiments performed on rats in the acute phase of SCI with Gd administered intravenously as a bolus. The time course and distribution of Gd concentration in injured spinal cord (SC) tissue and cerebrospinal fluid (CSF) were determined from intensity enhancements on the postcontrast T 1 -weighted images that were acquired sequentially. To represent the concentration data, a pharmacokinetic model was developed under limited permeability conditions for BSCB (6). This model consists of three compartments for plasma, injured cord, and CSF. Inclusion of a separate compartment for CSF was necessary because even though in humans CSF intensity remains nearly unchanged after Gd delivery in normal subjects, intensity enhances almost immediately in the CSF of normal rats (see the Discussion section). In this model, Gd transport between compartments was represented by different transfer rate constants. A window-based simulation analysis and modeling software was used to estimate the transfer parameters from the concentration data in plasma, CSF, and injured cord. The estimates associated with injured cord were ultimately used to evaluate the status of BSCB. Unlike the two-compartment pharmacokinetic models suggested specifically for studying BBB (4), the proposed model with three compartments takes into account the exchange of Gd between plasma and CSF. The utility of the model is discussed in the context of primary and secondary pathobiological processes that take place in the acute phase of SCI and the time window of opportunity for any therapeutic intervention. MATERIALS AND METHODS Animals and SCIA total of 11 (eight injured, two laminectomy controls, and one naïve control) male Sprague-Dawley rats weighing 350 -400 g were used...

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Spatial and temporal evolution of hemorrhage in the hyperacute phase of experimental spinal cord injury: In vivo magnetic resonance imaging

Cited by 64 publications

References 35 publications

The Early Evolution of Spinal Cord Lesions on MR Imaging following Traumatic Spinal Cord Injury

The Early Evolution of Spinal Cord Lesions on MR Imaging following Traumatic Spinal Cord Injury

Dynamic contrast‐enhanced MRI of experimental spinal cord injury: In vivo serial studies

A pharmacokinetic model for quantitative evaluation of spinal cord injury with dynamic contrast‐enhanced magnetic resonance imaging

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