I m a g i n g an d D e c i s i o n - M a k i n g i n N e u ro c r i t i c a l C a re Paul M. Vespa,
MD
KEYWORDS Traumatic brain injury Imaging modalities Central nervous system KEY POINTS There are several central nervous system–based neurocritical care disorders that are highly dependent on advanced imaging. Imaging modalities are very important in the diagnosis and treatment of traumatic brain injury. In contrast to conventional magnetic resonance imaging, proton-magnetic resonance spectroscopy documents evolutionary metabolic and neurochemical dysfunction after traumatic brain injury. Subarachnoid hemorrhage affects about 30,000 patients per year in the United States and even more worldwide. Intracerebral hemorrhage is a common disease with a substantial need for imaging.
INTRODUCTION
Critically ill neurologic patients are common in the hospital practice of neurology and are often in extreme states requiring accurate and specific information. Imaging, especially using advanced imaging techniques, can provide an important means of garnering this information. The reasons for this are many but do involve the lack of a clinical examination and the necessity to select treatments that are high risk but also high reward. This article focuses on the clinical utilization of selective imaging methods that are commonly used in critically ill neurologic patients to render diagnoses, to monitor effects of treatment, or have contributed to a better understanding of pathophysiology in the intensive care unit (ICU). The discussion focuses on clinical decision-making using neuroimaging and outlines the pitfalls and controversies of these techniques. NEUROCRITICAL CARE DISORDERS
There are several central nervous system–based neurocritical care disorders that are highly dependent on advanced imaging. These disorders include traumatic brain
David Geffen School of Medicine at UCLA, 757 Westwood Boulevard, Room 6236A, Los Angeles, CA 90095, USA E-mail address: [email protected] Neurol Clin 32 (2014) 211–224 http://dx.doi.org/10.1016/j.ncl.2013.07.010 neurologic.theclinics.com 0733-8619/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
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injury, stroke, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), status epilepticus, spinal cord injury, hypoxic-iscuemic coma, and hepatic coma. Most of these disorders share a common theme of a primary insult at the moment of injury or stroke followed by a progressive illness that rapidly worsens over a short period of time. During this progressive illness, cerebral edema, metabolic dysfunction, and ischemia may occur and this results in a secondary injury. The time course of secondary insults is many days if not weeks after the original injury. If the combination of the primary and secondary injuries is severe enough, long-term neurologic outcome will be poor. Therefore, the goals of neurocritical care are to forestall the secondary injuries and provide an opportunity for stabilization and recovery of function. These critical illnesses typically affect the brain in a heterogeneous fashion and hence imaging-based assessments of brain function are important, because imaging is capable of distinguishing regional brain structure and function. A common theme in comatose patients is the evolution of pathophysiology over several days. This pathophysiology typically involves early ischemia followed by evolving brain edema, cell death, and/or hydrocephalus. This evolving brain pathologic condition is difficult to monitor in the absence of neuroimaging and hence creates a requirement for serial imaging and strategic timed imaging. The timing of imaging is outlined on a disease-by-disease basis in the following text. IMAGING MODALITIES—RELEVANCE TO THE SPECIFIC DISORDERS Traumatic Brain Injury
Brain trauma is a very common neurocritical care illness, with over 500,000 patients affected each year, and at least 200,000 hospitalized with moderate-to-severe injuries. Imaging modalities are very important in the diagnosis and treatment of traumatic brain injury (TBI). Principal among these are magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), computed tomography (CT), and positron emission tomography (PET) imaging. CT scanning is commonly used to screen patients for moderate to severe injury and to triage patients to surgery rapidly. Noncontrast CT is best used for serial imaging in TBI. The purpose of CT in TBI is to detect surgical lesions and cerebral edema. Fig. 1 outlines several important lesion types in acute TBI. CT is typically performed on an emergency basis and is then repeated periodically during the ICU stay to detect brain edema. Table 1 outlines the use of CT, including the timing and potential adjustments in clinical care that ensues. Cerebral edema can be evaluated and medical treatment can be titrated based on the CT findings. Special attention to midline shift, compression of the cisterns, and mass effect from hemorrhages can be helpful to the intensivist and can guide treatment. For example, an increase in hemorrhage volume, as shown in Fig. 2, could be used to make a decision about intracranial pressure monitoring or decompressive surgery. Clinical prognostication using the Marshall grading system has become commonplace and is an important component of the Project-Impact prognostic scoring system.1 It is recognized that there is variability in interpretation of these scans, and the clinician is advised to review these scans personally for evolution of brain edema, using the Marshall grading scale (Table 2). MRI
The important MRI sequences for the assessment of TBI include gradient echo recall, signal-weighted intensity, fluid attenuation inversion recovery, and diffusion tensor imaging (DTI). Using MRI, permanent injuries have been widely documented: (1) MRI is able to detect an increased number of subcortical injuries that are not apparent on conventional computerized tomography.2–5 (2) Diffuse shear injuries occur but are
Imaging and Decision-Making in Neurocritical Care
Fig. 1. CT of brain lesions.
not uniformly hemorrhagic.2 (3) Many areas of the brain appear quite normal without evidence of edema or structural change.6–8 (4) The location and number of deep shearing injuries are correlated with poor outcome, with lesions of the corpus callosum and dorsal brainstem having particularly negative influence on outcome.2,6,9 The
Table 1 Imaging clinical protocol in traumatic brain injury in the ICU Imaging Test
Frequency
Interpretative Queries ICU Treatment Decision
Noncontrast CT PIH 1, 6, 12
Surgical lesion Progressive edema Elevated ICP
Surgical decompression ICP/EVD monitor Osmolar therapy
Noncontrast CT PIH 72 or 96
Progressive edema Hydrocephalus
Surgical decompression Osmolar therapy Tapering EVD
CTA
PIH 6 and clinical Vascular injury suspicion
Endovascular or surgical treatment of vascular injury
MRI
PID 1–7
Lesion location and total lesion burden
Prognostic assessment Osmolar therapy Treat ongoing ischemia
MRS
PID 1–7
Metabolic function of the brain
Prognostic assessment
PET
PID 1–7
Metabolic function of the brain
Research tool at present; glucose control and CO2 control
Abbreviations: EVD, external ventricular drain; ICP, intracranial pressure; PID, post injury day; PIH, post injury hour.
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Fig. 2. Evolution and expansion of traumatic brain hemorrhage.
extent of these acute brain lesions suggests that a small portion of the brain has some element of injury because of the deep shear lesions or brain edema, whereas many regions on MRI demonstrate no apparent injury at all. Special sequences such as the susceptibility weighted image provide enhanced detection of magnetic field inhomogeneity, which results in increased signal attenuation in regions of brain hemorrhage and is useful for detecting microhemorrhages that are caused by traumatic axonal injury. Fig. 3 demonstrates the typical appearance of many small traumatic hemorrhages in a patient with severe TBI. DTI
DTI is widely being applied to acute stroke for the determination of early stroke location and vascular anatomy definitions and is covered elsewhere in this issue. DTI is also being applied to patients with hypoxic ischemic injury (HIE), and TBI. In HIE, there are early diffuse signs of cortical and subcortical diffusion restriction that can make the diagnosis of ischemic brain injury. In TBI, DTI in the form of tractography and fractional
Table 2 Major CT imaging designation using the Marshall classification Marshall Class
Finding
Diffuse injury type 1
No visible lesion
Clinical Significance Low likelihood of ICP
Diffuse injury type II
Cisterns present Midline shift 0–5 mm No high density lesion >25 mL
Moderate likelihood of ICP
Diffuse injury type III
Cisterns compressed or absent with midline shift 0–5 mm No high-density or mixed-density lesion >25 mL
High likelihood of ICP Deeper coma
Diffuse injury type IV
Cistersn compressed Midline shift >5 mm High-density or mixed-density lesion >25 mL
High likelihood of ICP Deeper coma
Nonevacuated mass lesion
Mass lesion remains
High likelihood of ICP Deeper coma
Evacuated mass lesion
Mass lesion removed
Variable ICP
Imaging and Decision-Making in Neurocritical Care
Fig. 3. Example of traumatic axonal injury detected by MRI.
anisotropy (FA) is being used to evaluate mild TBI and can be useful in moderate and severe TBI. However, the use of DTI in TBI is somewhat less applicable to clinical practice at this time. Recently, DTI imaging has been used for the description of white matter injuries. The main measure is that of FA. FA is typically reduced after TBI, due to tissue edema in white matter or to traumatic axonal injury, resulting in subtle findings on visible MRI. Quantitative measures are required to detect reductions in FA. Threedimensional imaging transforms DTI measures into visible tractography through a variety of methods, many of which are automated in clinical MRI instruments. Fig. 4 demonstrates an example of tractogram image in severe TBI. With severe brain injury, the white matter tracts are disrupted and loss of vector-related tracts can be seen. MRS
In contrast to conventional MRI, proton-magnetic resonance spectroscopy (H-MRS) documents evolutionary metabolic and neurochemical dysfunction after TBI. H-MRS has the ability to detect concentrations of several metabolites that become reversibly abnormal after TBI. The abnormal metabolic profile includes a reduction in levels of NAA (n-acetyl-aspartate), NAA/Cho (NAA/choline) and NAA/Cr levels (NAA/creatine). In nontraumatized normal adults, the normal values are as follows: NAA 10 mmol/L 0.9, Cr 6.0 1.3, Cho 1.6 0.3, and for ratios normal values are NAA/Cr >4, NAA/Cho >3, and Cho/Cr >1.5.10–13 There is some age-related decrease in NAA with a lower limit of normal 7 0.6 in patients greater than 70 years. Values are reduced after TBI in both normal-appearing white matter and pericontusional tissue and these reductions persist for weeks to months. Most changes are related to a
Fig. 4. Diffusion tensor tractography in acute brain injury. (A) Sagittal image showing long fiber tracts, (B) Axial image showing white matter connecting fiber tracts, (C) Coronal image showing crossing and long fiber tracts.
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primary reduction in NAA and increase in Cho without significant change in Cr levels. NAA reductions in mild TBI have been used to document metabolic dysfunction in the normal-appearing white matter despite a lack of structural MRI findings. MRS NAA levels have been correlated with 6-month outcome after mild to moderate TBI.14–16 The MRS neurochemical abnormalities are in part reversible and exhibit a predictable time course of resolution. A limited number of studies have combined early imaging (
MD
KEYWORDS Traumatic brain injury Imaging modalities Central nervous system KEY POINTS There are several central nervous system–based neurocritical care disorders that are highly dependent on advanced imaging. Imaging modalities are very important in the diagnosis and treatment of traumatic brain injury. In contrast to conventional magnetic resonance imaging, proton-magnetic resonance spectroscopy documents evolutionary metabolic and neurochemical dysfunction after traumatic brain injury. Subarachnoid hemorrhage affects about 30,000 patients per year in the United States and even more worldwide. Intracerebral hemorrhage is a common disease with a substantial need for imaging.
INTRODUCTION
Critically ill neurologic patients are common in the hospital practice of neurology and are often in extreme states requiring accurate and specific information. Imaging, especially using advanced imaging techniques, can provide an important means of garnering this information. The reasons for this are many but do involve the lack of a clinical examination and the necessity to select treatments that are high risk but also high reward. This article focuses on the clinical utilization of selective imaging methods that are commonly used in critically ill neurologic patients to render diagnoses, to monitor effects of treatment, or have contributed to a better understanding of pathophysiology in the intensive care unit (ICU). The discussion focuses on clinical decision-making using neuroimaging and outlines the pitfalls and controversies of these techniques. NEUROCRITICAL CARE DISORDERS
There are several central nervous system–based neurocritical care disorders that are highly dependent on advanced imaging. These disorders include traumatic brain
David Geffen School of Medicine at UCLA, 757 Westwood Boulevard, Room 6236A, Los Angeles, CA 90095, USA E-mail address: [email protected] Neurol Clin 32 (2014) 211–224 http://dx.doi.org/10.1016/j.ncl.2013.07.010 neurologic.theclinics.com 0733-8619/14/$ – see front matter Ó 2014 Elsevier Inc. All rights reserved.
212
Vespa
injury, stroke, intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), status epilepticus, spinal cord injury, hypoxic-iscuemic coma, and hepatic coma. Most of these disorders share a common theme of a primary insult at the moment of injury or stroke followed by a progressive illness that rapidly worsens over a short period of time. During this progressive illness, cerebral edema, metabolic dysfunction, and ischemia may occur and this results in a secondary injury. The time course of secondary insults is many days if not weeks after the original injury. If the combination of the primary and secondary injuries is severe enough, long-term neurologic outcome will be poor. Therefore, the goals of neurocritical care are to forestall the secondary injuries and provide an opportunity for stabilization and recovery of function. These critical illnesses typically affect the brain in a heterogeneous fashion and hence imaging-based assessments of brain function are important, because imaging is capable of distinguishing regional brain structure and function. A common theme in comatose patients is the evolution of pathophysiology over several days. This pathophysiology typically involves early ischemia followed by evolving brain edema, cell death, and/or hydrocephalus. This evolving brain pathologic condition is difficult to monitor in the absence of neuroimaging and hence creates a requirement for serial imaging and strategic timed imaging. The timing of imaging is outlined on a disease-by-disease basis in the following text. IMAGING MODALITIES—RELEVANCE TO THE SPECIFIC DISORDERS Traumatic Brain Injury
Brain trauma is a very common neurocritical care illness, with over 500,000 patients affected each year, and at least 200,000 hospitalized with moderate-to-severe injuries. Imaging modalities are very important in the diagnosis and treatment of traumatic brain injury (TBI). Principal among these are magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), computed tomography (CT), and positron emission tomography (PET) imaging. CT scanning is commonly used to screen patients for moderate to severe injury and to triage patients to surgery rapidly. Noncontrast CT is best used for serial imaging in TBI. The purpose of CT in TBI is to detect surgical lesions and cerebral edema. Fig. 1 outlines several important lesion types in acute TBI. CT is typically performed on an emergency basis and is then repeated periodically during the ICU stay to detect brain edema. Table 1 outlines the use of CT, including the timing and potential adjustments in clinical care that ensues. Cerebral edema can be evaluated and medical treatment can be titrated based on the CT findings. Special attention to midline shift, compression of the cisterns, and mass effect from hemorrhages can be helpful to the intensivist and can guide treatment. For example, an increase in hemorrhage volume, as shown in Fig. 2, could be used to make a decision about intracranial pressure monitoring or decompressive surgery. Clinical prognostication using the Marshall grading system has become commonplace and is an important component of the Project-Impact prognostic scoring system.1 It is recognized that there is variability in interpretation of these scans, and the clinician is advised to review these scans personally for evolution of brain edema, using the Marshall grading scale (Table 2). MRI
The important MRI sequences for the assessment of TBI include gradient echo recall, signal-weighted intensity, fluid attenuation inversion recovery, and diffusion tensor imaging (DTI). Using MRI, permanent injuries have been widely documented: (1) MRI is able to detect an increased number of subcortical injuries that are not apparent on conventional computerized tomography.2–5 (2) Diffuse shear injuries occur but are
Imaging and Decision-Making in Neurocritical Care
Fig. 1. CT of brain lesions.
not uniformly hemorrhagic.2 (3) Many areas of the brain appear quite normal without evidence of edema or structural change.6–8 (4) The location and number of deep shearing injuries are correlated with poor outcome, with lesions of the corpus callosum and dorsal brainstem having particularly negative influence on outcome.2,6,9 The
Table 1 Imaging clinical protocol in traumatic brain injury in the ICU Imaging Test
Frequency
Interpretative Queries ICU Treatment Decision
Noncontrast CT PIH 1, 6, 12
Surgical lesion Progressive edema Elevated ICP
Surgical decompression ICP/EVD monitor Osmolar therapy
Noncontrast CT PIH 72 or 96
Progressive edema Hydrocephalus
Surgical decompression Osmolar therapy Tapering EVD
CTA
PIH 6 and clinical Vascular injury suspicion
Endovascular or surgical treatment of vascular injury
MRI
PID 1–7
Lesion location and total lesion burden
Prognostic assessment Osmolar therapy Treat ongoing ischemia
MRS
PID 1–7
Metabolic function of the brain
Prognostic assessment
PET
PID 1–7
Metabolic function of the brain
Research tool at present; glucose control and CO2 control
Abbreviations: EVD, external ventricular drain; ICP, intracranial pressure; PID, post injury day; PIH, post injury hour.
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Fig. 2. Evolution and expansion of traumatic brain hemorrhage.
extent of these acute brain lesions suggests that a small portion of the brain has some element of injury because of the deep shear lesions or brain edema, whereas many regions on MRI demonstrate no apparent injury at all. Special sequences such as the susceptibility weighted image provide enhanced detection of magnetic field inhomogeneity, which results in increased signal attenuation in regions of brain hemorrhage and is useful for detecting microhemorrhages that are caused by traumatic axonal injury. Fig. 3 demonstrates the typical appearance of many small traumatic hemorrhages in a patient with severe TBI. DTI
DTI is widely being applied to acute stroke for the determination of early stroke location and vascular anatomy definitions and is covered elsewhere in this issue. DTI is also being applied to patients with hypoxic ischemic injury (HIE), and TBI. In HIE, there are early diffuse signs of cortical and subcortical diffusion restriction that can make the diagnosis of ischemic brain injury. In TBI, DTI in the form of tractography and fractional
Table 2 Major CT imaging designation using the Marshall classification Marshall Class
Finding
Diffuse injury type 1
No visible lesion
Clinical Significance Low likelihood of ICP
Diffuse injury type II
Cisterns present Midline shift 0–5 mm No high density lesion >25 mL
Moderate likelihood of ICP
Diffuse injury type III
Cisterns compressed or absent with midline shift 0–5 mm No high-density or mixed-density lesion >25 mL
High likelihood of ICP Deeper coma
Diffuse injury type IV
Cistersn compressed Midline shift >5 mm High-density or mixed-density lesion >25 mL
High likelihood of ICP Deeper coma
Nonevacuated mass lesion
Mass lesion remains
High likelihood of ICP Deeper coma
Evacuated mass lesion
Mass lesion removed
Variable ICP
Imaging and Decision-Making in Neurocritical Care
Fig. 3. Example of traumatic axonal injury detected by MRI.
anisotropy (FA) is being used to evaluate mild TBI and can be useful in moderate and severe TBI. However, the use of DTI in TBI is somewhat less applicable to clinical practice at this time. Recently, DTI imaging has been used for the description of white matter injuries. The main measure is that of FA. FA is typically reduced after TBI, due to tissue edema in white matter or to traumatic axonal injury, resulting in subtle findings on visible MRI. Quantitative measures are required to detect reductions in FA. Threedimensional imaging transforms DTI measures into visible tractography through a variety of methods, many of which are automated in clinical MRI instruments. Fig. 4 demonstrates an example of tractogram image in severe TBI. With severe brain injury, the white matter tracts are disrupted and loss of vector-related tracts can be seen. MRS
In contrast to conventional MRI, proton-magnetic resonance spectroscopy (H-MRS) documents evolutionary metabolic and neurochemical dysfunction after TBI. H-MRS has the ability to detect concentrations of several metabolites that become reversibly abnormal after TBI. The abnormal metabolic profile includes a reduction in levels of NAA (n-acetyl-aspartate), NAA/Cho (NAA/choline) and NAA/Cr levels (NAA/creatine). In nontraumatized normal adults, the normal values are as follows: NAA 10 mmol/L 0.9, Cr 6.0 1.3, Cho 1.6 0.3, and for ratios normal values are NAA/Cr >4, NAA/Cho >3, and Cho/Cr >1.5.10–13 There is some age-related decrease in NAA with a lower limit of normal 7 0.6 in patients greater than 70 years. Values are reduced after TBI in both normal-appearing white matter and pericontusional tissue and these reductions persist for weeks to months. Most changes are related to a
Fig. 4. Diffusion tensor tractography in acute brain injury. (A) Sagittal image showing long fiber tracts, (B) Axial image showing white matter connecting fiber tracts, (C) Coronal image showing crossing and long fiber tracts.
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primary reduction in NAA and increase in Cho without significant change in Cr levels. NAA reductions in mild TBI have been used to document metabolic dysfunction in the normal-appearing white matter despite a lack of structural MRI findings. MRS NAA levels have been correlated with 6-month outcome after mild to moderate TBI.14–16 The MRS neurochemical abnormalities are in part reversible and exhibit a predictable time course of resolution. A limited number of studies have combined early imaging (
