Neuroimaging in the Assessment of 

Traumatic Brain Injury (TBI), Mild 

TBI, and PTSD*

David H. Salat, PhD

Neuroimaging Research for Veterans Center (NeRVe) 

Translational Research Center for TBI and Stress Disorders (TRACTS)

VA Boston Healthcare System

Athinoula A. Martinos Center for Biomedical Imaging, MGH Radiology

VHA Cyberseminar

05/28/2014

*A very limited presentation of some examples in the literature
Poll Question #1

• What is your primary role in VA? 

– student, trainee, or fellow

– clinician

– researcher 

– manager or policy-maker 

– Other 
Poll Question #1

• What is your primary role in VA? 

– student, trainee, or fellow

– clinician

– researcher 

– manager or policy-maker 

– Other 
Poll Question #2

• Which best describes your research 

experience?

– have not done research

– have collaborated on research

– have conducted research myself

– have applied for research funding

– have led a funded research grant
Poll Question #3

• If you have performed imaging research, what 

domain did you work in (check all that apply)?

– Structural

– Diffusion imaging

– Functional Imaging (task/resting)

– CT

– MRI

– PET 

– EEG/MEG

– Other 
Poll Question #3

• If you have performed imaging research, what 

domain did you work in (check all that apply)?

– Structural

– Diffusion imaging

– Functional Imaging (task/resting)

– CT

– MRI

– PET 

– EEG/MEG

– Other 
Scope of the Problem

• Much existing epidemiology is either prior to or does not have 

information of the full impact of recent conflicts

• Discussion of imaging TBI generally including information 

from civilian as well as military populations, across a range of 

severity

• Thurman et al., 1999; Kraus, 1996; Ruff et al., 2009; Centers for 

Disease Control and Prevention:

– Annual incidence of ~1.5 million TBIs

– ~80% considered ‘mild’

– ~20% moderate to severe

– ~50,000 die

– ~230,000 hospitalized

– ~80,000–90,000 long-term disability

• Large economic burden
What is a ‘Diagnosis’ of TBI?

• Diagnosis and definition of TBI differs clinically and 

across research studies, but typically based on:

– Information about the syndrome at time of the event 

• loss of consciousness, retrograde and post-traumatic amnesia, 

disorientation and confusion (Ruff et al., 2009) 

– Neurological signs: focal signs, seizure, and/or intracranial 

lesion (e.g., contusion, hematoma, hemorrhage, or edema) 

– Standardized Scales:

• Glasgow Coma Scale (GCS) (Teasdale and Jennett, 1974; Jennett, 

1998):

– Motor, verbal, eye responses

– <8: severe, 9-12: moderate, 13 to 15: mild 
What is the ‘Brain Injury’ in TBI?

• Anterior cortex vulnerable to damage (Adams et 

al., 1980; Levin et al., 1996)

• Axonal injury due to linear and rotational forces 

(Buki and Povlishock, 2006; Gennarelli et al., 

1982; Meythaler et al., 2001; Povlishock et al., 

1992) 

• Secondary biochemical, cellular, metabolic, 

cascades (minutes, days and months) (Giza and 

Hovda, 2001; Loane and Faden, 2010; Xiong et 

al., 1997)
Common Moderate/Severe TBIAssociated Pathology

• Contusion: blood vessels damaged by trauma; blood 

invades surrounding interstitial tissue resulting in necrosis

• Laceration: membranes are torn over the site of injury

• Herniation: mass effect and increase in intracranial 

pressure (due to above); life-threatening due to pressure of 

tissue to skull

• Axonal injury/diffuse axonal injury: Damage to fibers in 

cerebral white matter

• Cerebral swelling: Edema/extra/intracellular fluid 

accumulation

• Intraventricular hemorrhage: Bleeding into the ventricular 

system
Concussion and ‘Mild’ TBI

• Concussion: “A complex pathophysiological process affecting the brain, induced by 

traumatic biomechanical forces.“ (Cantu 2006; McCrory et al., 2013)

• Often used synonymously with mTBI (e.g. Ruff et al., 2009)

• Head injury with temporary loss of ‘brain function’

– Loss or ‘change’ in consciousness: Amnesia/Glasgow Coma Scale

• Graded depending on:

– Loss of consciousness: present/absent

– Duration of changes in mental status post event

• Symptoms typically resolve in weeks

• Absence of gross structural changes on ‘conventional’ imaging is may be diagnostic

– “Complicated mTBI”: mTBI with abnormal neuroimaging

• Cumulative effect of multiple concussions/long-term consequences (Guskiewicz et 

al., 2003).

• Potentially linked to secondary consequences including neurodegenerative disease 

and dementia 
TBI Is Heterogeneous

• Type of exposure?

• Force of exposure?

• Direction of exposure?

• Time since exposure?

• Time-course of injury?
Is Military/Combat-Associated TBI 

Unique? 

• Combat-associated blast exposure is highly 

prevalent (Okie 2005)

• Patients admitted to Walter Reed who have 

been exposed to a blast evaluated for brain 

injury: 

– 59% TBI diagnosis

• 56% moderate or severe TBI

• 44% mild
Mechanisms of Blast Injury

Taber et al., 2006

• Brain injuries occur:

– Direct result of blast waveinduced changes in 

atmospheric pressure 

(barotrauma/primary blast 

injury)

– Objects put in motion by the 

blast (secondary blast injury)

– People being forcefully put in 

motion by the blast (tertiary 

blast injury) 

• Stress and shear waves
Nonpenetrating Injuries

Taber et al., 2006
What does clinical imaging contribute?

• Computed tomography (CT) of the head is the 

study of choice to evaluate TBI (Brown et al., 

2004) 

• Evaluate need for surgical intervention

• Repeat CT in patients with a neurologic 

deterioration after TBI for assessment of injury 

progression (Patel et al., 2000)

• Classification of injury by pathophysiologic 

mechanisms for targeted by interventions 

(Saatman et al., 2008)
Classification of Injury by CT

• Most often clinically for first 24 hours after injury

• ‘X-Ray’ imaging

• Edema/infarction: dark

• Calcifications, hemorrhage, bone trauma: 

bright

• Pros:

– Available, cost effective, short imaging times, 

can be performed with life support hardware, 

implants, sharpnel, etc.

– Most appropriate for determining immediate 

medical needs

• Cons:

– Reduced resolution

– Limited contrast/information

– Ionizing radiation (considered moderate to 

high)

• Lack of imaging findings on CT may be used 

to classify ‘mild’ TBI

• CT findings may not be correlated with 

outcome

Epidural hematomas (EDH), contusions and 

parenchymal hematomas (Contusion/Hematoma),

diffuse axonal injury (DAI), subdural hematoma (SDH), 

subarachnoid hemorrhage and intraventricular

hemorrhage (SAH/IVH),

and diffuse brain swelling (Diffuse Swelling): From 

Saatman, et al, J Neurotrauma, 2008
Clinical Imaging: MRI

• Edema: bright on T2/FLAIR MRI

• Hemorrhage: time-course from bright to dark 

to bright again

• Microhemorrhage: gradient echo MRI
What can research neuroimaging 

contribute? 

• A range of imaging procedures exist that may not be practical for routine clinical assessment, but 

may provide valuable information for:

– Future diagnostics

– Tracking injury progression

– Tracking novel therapeutic interventions

– Understanding mechanisms of injury

• Different imaging modalities that vary in spatial and temporal resolution and contrast mechanisms

• Research imaging procedures may target specific aspects of brain tissue structure, function, 

physiology or chemistry

• Various ways to process and analyze data

– ‘Group’-based comparisons to control populations

– Association between imaging findings and neuropsychological and clinical scales

• Particular application to mTBI where conventional imaging findings are 

limited

• Significant effort, yet limited consistent information about mTBI based on 

imaging

• Present procedures and trends as opposed to detailed information about 

work to date
Research Imaging

‘Structural’

• Structural/Morphometry (T1- MRI) 

– Volume, thickness, curvature etc.

• ‘Lesion’ or abnormal tissue (e.g. 

edema) (T2/FLAIR-MRI) 

• ‘Microstructural’

– Diffusion tensor imaging (DTI)

– Magnetization transfer imaging 

(MTI)

– Relaxometry

• Receptor/protein densities (Positron 

Emission Tomography; PET radioligands) 

• ‘Susceptibility’ weighted imaging: 

Hemorrhage/axonal injury 

‘Functional’

• Brain ‘activity’

– Functional magnetic resonance 

imaging (fMRI)

– Electroencephalography

– Magnetoencephalography 

– PET

• Glucose metabolism

• CMRO2

• Magnetic resonance 

spectroscopy (MRS)

• Cerebral blood flow

– Arterial spin labeling (ASL) 

– PET
Recent mTBI Publication Expansion

Eierud et al., 2014
Diffusion Weighted/Tensor Imaging 

(DWI/DTI) 

• Magnetic Resonance Imaging (MRI) procedure

• Quantification of diffusion of molecules (water) in tissue

• Water diffusion in tissue is influenced by macromolecules, 

membranes, tends to follow fibers

• Diffusion measures can modeled to provide information about 

tissue ‘microstructural’ properties

• Extensions of DWI such as DTI provide information that can be used 

to model the anatomy of large fiber bundles

• Different ways of modeling the diffusion data providing different 

types of ‘contrast’ linked to tissue properties

• ‘Axial’ versus ‘radial’ diffusivity

• In vivo and non-invasive 

• Thought to be potentially sensitive to diffuse axonal injury

• See Le Bihan and Johansen-Berg 2012 for recent review
Diffusion ‘Maps’

Microstructure: Fractional 

Anisotropy Anatomy: Tensormap
Example: DTI in mTBI 

Lipton et al., 2009

• DTI and neuropsychologic

assessment in 20 patients with 

mTBI within 2 weeks of injury

• mTBI due to motor vehicle 

accidents or falls and were 

evaluated to rule out 

conventional brain injury

• Whole brain analysis of DTI 

parameters

• Clusters of lower frontal white 

matter FA/higher MD

• Lower dorsolateral prefrontal FA 

correlated with worse executive 

function 
Example: Blast mTBI 

Levin et al., 2010

• 37 veterans/service members

• Post-injury interval 871.5 days

• Mild to moderate blast TBI

• Standard ‘region-of-interest’ 

and ‘voxel-based’ analysis 

showed no group difference

• Regional diffusion measures 

associated with total words 

consistently recalled 

• Correlations of DTI variables 

with symptom measures were 

nonsignificant and 

inconsistent. 
Meta-analysis of Diffusion Findings

Eierud et al., 2014
Complicated Diffusion Timecourse? 

• Anisotropy is increased in the acute phase and 

decreased in the chronic phase in 

symptomatic TBI (Niogi and Mukherjee, 2010) 

• Animal models demonstrate changes in 

diffusion signal hours to weeks or longer after 

injury (e.g. Assaf et al., 1997; Albensi et al., 

2000)
Functional MRI (fMRI)

• Used to measure brain 

‘activity’

• Contrast based on blood 

oxygenation 

• Signal can be measured in 

response to cognitive or 

behavioral stimuli 

‘hemodynamic response’ 

• In the ‘resting’ state

Riecker et al., 2003
Example: fMRI/DTI in Blast mTBI 

Matthews et al., 2007

• 11 MDD and 11 non-MDD

• Emotional face matching fMRI

task

• DTI

• MDD had greater amygdala 

activity during fear matching 

trials

• lower activity during fear 

matching trials in emotional 

control structures (DLPFC)

• Lower diffusion measures in SLF

• Depressive symptom severity 

associated with SLF integrity
Meta-analysis of fMRI Findings

Eierud et al., 2014

• ‘Anterior-to-posterior’ pattern: 

reduced in anterior regions 

and increased in posterior 

regions

• Six regions consistently more 

active in mTBI

– MFG, ACC, and right precentral

gyrus 

• Seven regions with lower 

activity in mTBI

– Cerebellum/insula/parietal (BA 

40) 
Positron Emission Tomography (PET)

• Nuclear medicine technique

• Detection of gamma rays 

emitted by a positron- emitting radionuclide 

• Radionucleotide (PET 

ligand) is a biologically 

active molecule injected 

into the body (invasive)

• Can be used to measure 

receptor concentrations, 

metabolic activity (FDG), 

blood flow, inflammation 

(diverse contrast)

• MGH Radiology Rounds:

– http://www.mghradrounds.org/index.p

hp?src=gendocs&link=2006_april
Example: PET/FDG in mTBI 

Peskind et al., 2011

• 12 Iraq war Veterans

• one or more blast exposures

• Diagnosis of mTBI and persistent 

PCS

• 12 cognitively normal community 

volunteers without head trauma

• FDG PET tomography (FDG-PET)

• Neuropsychological/clinical 

assessment

• mTBI had decreased cerebral 

metabolic rate of glucose in the 

cerebellum, vermis, pons, and 

medial temporal lobe
TRACTS

• ‘Translational Research Center for TBI and 

Stress Disorders’

• A Rehabilitation Research and Development 

Center of Excellence, Director: McGlinchey

• Goal: Understand the complex changes in the 

brain, thinking, and psychological well-being 

that result from TBI and PTSD

• Veterans from Operation Enduring Freedom, 

Operation Iraqi Freedom (OEF/OIF)
Morphometry: Cortical Thickness
Example: Cortical Thickness, PTSD, and 

mTBI 

Lindemer et al., 2013

• 104 OEF/OIF veterans

• PTSD symptoms assessed: Clinician 

Administered PTSD Scale (CAPS): previous 

month (“current”)

• Cumulative Lifetime Burden of 

PTSD/integration of lifetime CAPS scores

• Mild TBI: Boston Assessment of TBI-Lifetime 

(BAT-L) 

• Negative relationship between current

• PTSD severity and thickness

• Stronger association when lifetime burden 

was considered

• Stronger regional associations in individuals 

with mTBI

• Various factors (e.g. lifetime stress; mTBI) 

interact and demonstrate need for extremely 

well matched groups or very large cohorts
But TBI Is Heterogeneous

• Type of exposure?

• Force of exposure?

• Direction of exposure?

• Time since exposure?

• Time-course of injury?
Imaging Groups or Individuals?

Davenport et al., 2012

• American military service members 

with (n=25) or without (n=33) blast- related mTBI

• Individuals with more than one blast 

mTBI had greater number of low FA 

voxels than individuals with a single 

blast injury

• Effects were not apparent when using 

‘region of interest’ procedure

• Blast mTBI is associated with disrupted 

integrity of several white matter tracts 

• Findings are diluted by averaging across 

the large number of voxels within an 

ROI

• Neurological effects of blast mTBI are 

diffuse, widespread, and spatially 

variable
Caveats to Neuroimaging TBI

• Who are the study participants?

– Premorbid conditions?

• Prior psychological or physical trauma?

• Medical comorbidities?

• Drug and alcohol use?

• What type of TBI?

– Blast?

– Blunt?

– Mild, moderate, severe?

• How was the TBI diagnosed?

– GCS?

– +/- Imaging?

• Time since injury?

– Acute?

– Chronic?

• Mechanism of injury?

– Primary?

– Secondary?

– Interaction with comorbidities/genetics?

• Any given finding in neuroimaging may be 

limited to a very specific population and not 

generalizable to overall TBI

• Imaging techniques are indirect

• The mechanistic basis of any imaging finding 

can be complex

• Imaging procedures can be influenced by 

various technical limitations resulting in 

artifactual results

• Many tests are performed with imaging data 

increasing the likelihood of statistical error

• Small participant samples can lead to 

spurious results
Conclusions

• Eierud et al., 2014
Conclusions

• Neuroimaging provides a window into brain 

pathology

• Procedures facilitate measurement of brain 

structure, function, tissue integrity, metabolism, 

chemistry and other aspects of physiology

• Potential to uncover mechanisms of TBI- associated cognitive, behavioral, and psychiatric 

conditions

• Advances in novel acquisition and analysis 

procedures, participant characterization, and 

multimodal image integration will be necessary
Acknowledgements

• Department of Veterans Affairs Rehabilitation 

Research & Development Service 

• Translational Research Center for TBI and Stress 

Disorders

• Neuroimaging Research for Veterans Center, VA 

Boston

• Terence Keane, PhD

• Gina McGlinchey, PhD

• Bill Milberg, PhD
Questions?

• David.Salat@va.gov
References/Suggested Reading 1

• Adams, J.H., Graham, D.I., Scott, G., Parker, L.S., Doyle, D., 1980. Brain damage in fatal non-missile head injury. J Clin Pathol

33, 1132-1145.

• Albensi, B.C., Knoblach, S.M., Chew, B.G., O'Reilly, M.P., Faden, A.I., Pekar, J.J., 2000. Diffusion and high resolution MRI of 

traumatic brain injury in rats: time course and correlation with histology. Exp Neurol 162, 61-72.

• Assaf, Y., Beit-Yannai, E., Shohami, E., Berman, E., Cohen, Y., 1997. Diffusion- and T2-weighted MRI of closed-head injury in 

rats: a time course study and correlation with histology. Magn Reson Imaging 15, 77-85.

• Brown, C.V., Weng, J., Oh, D., Salim, A., Kasotakis, G., Demetriades, D., Velmahos, G.C., Rhee, P., 2004. Does routine serial 

computed tomography of the head influence management of traumatic brain injury? A prospective evaluation. J Trauma 57, 

939-943.

• Cantu, R.C., Aubry, M., Dvorak, J., Graf-Baumann, T., Johnston, K., Kelly, J., Lovell, M., McCrory, P., Meeuwisse, W., 

Schamasch, P., Kevin, M., Bruce, S.L., Ferrara, M.S., Kelly, J.P., McCrea, M., Putukian, M., McLeod, T.C., 2006. Overview of 

concussion consensus statements since 2000. Neurosurg Focus 21, E3.

• Davenport, N.D., Lim, K.O., Armstrong, M.T., Sponheim, S.R., 2012. Diffuse and spatially variable white matter disruptions are 

associated with blast-related mild traumatic brain injury. Neuroimage 59, 2017-2024.

• Division of Injury and Disability Outcomes and Programs National Center for Injury Prevention and Control Centers for 

Disease Control and Prevention Department of Health and Human Services, 2004. Traumatic Brain Injury in the United 

States: Emergency Department Visits, Hospitalizations, and Deaths.

• Eierud, C., Craddock, C.R., Fletcher, S., Aulakhe, M., King-Casas, B., Kuehl, D., LaConte, S.M., 2014. Neuroimaging after mild 

traumatic brain injury: Review and meta-analysis. NeuroImage: Clinical 4, 283-294. 
References/Suggested Reading 2

• Giza, C.C., Hovda, D.A., 2001. The Neurometabolic Cascade of Concussion. J Athl Train 36, 228-235.

• Guskiewicz, K.M., McCrea, M., Marshall, S.W., Cantu, R.C., Randolph, C., Barr, W., Onate, J.A., Kelly, J.P., 2003. Cumulative 

effects associated with recurrent concussion in collegiate football players: the NCAA Concussion Study. JAMA 290, 2549-

2555.

• Jennett, B., 1998. Epidemiology of head injury. Arch Dis Child 78, 403-406.

• Kraus, J.F., McArthur, D.L., Silverman, T.A., Jayaraman, M., 1996. Epidemiology of brain injury. In: Naravan, R.K., Wilberger, 

J.E., Povlishock, J.T. (Eds.), Neurotrauma. McGraw-Hill, New York.

• Le Bihan, D., Johansen-Berg, H., 2012. Diffusion MRI at 25: exploring brain tissue structure and function. Neuroimage 61, 

324-341.

• Levin, H., Kraus, M.F., 1994. The frontal lobes and traumatic brain injury. J Neuropsychiatry Clin Neurosci 6, 443-454.

• Levin, H.S., Wilde, E., Troyanskaya, M., Petersen, N.J., Scheibel, R., Newsome, M., Radaideh, M., Wu, T., Yallampalli, R., Chu, 

Z., Li, X., 2010. Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae. J 

Neurotrauma 27, 683-694.

• Lindemer, E.R., Salat, D.H., Leritz, E.C., McGlinchey, R.E., Milberg, W.P., 2013. Reduced cortical thickness with increased 

lifetime burden of PTSD in OEF/OIF Veterans and the impact of comorbid TBI. Neuroimage Clin 2, 601-611.

• Lipton, M.L., Gulko, E., Zimmerman, M.E., Friedman, B.W., Kim, M., Gellella, E., Gold, T., Shifteh, K., Ardekani, B.A., Branch, 

C.A., 2009. Diffusion-tensor imaging implicates prefrontal axonal injury in executive function impairment following very mild 

traumatic brain injury. Radiology 252, 816-824.

• Loane, D.J., Faden, A.I., 2010. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic 

strategies. Trends Pharmacol Sci 31, 596-604.
References/Suggested Reading 3

• Matthews, S.C., Strigo, I.A., Simmons, A.N., O'Connell, R.M., Reinhardt, L.E., Moseley, S.A., 2011. A multimodal imaging study 

in U.S. veterans of Operations Iraqi and Enduring Freedom with and without major depression after blast-related concussion. 

Neuroimage 54 Suppl 1, S69-75.

• McCrory, P., Meeuwisse, W., Aubry, M., Cantu, B., Dvorak, J., Echemendia, R., Engebretsen, L., Johnston, K., Kutcher, J., 

Raftery, M., Sills, A., Benson, B., Davis, G., Ellenbogen, R., Guskiewicz, K., Herring, S.A., Iverson, G., Jordan, B., Kissick, J., 

McCrea, M., McIntosh, A., Maddocks, D., Makdissi, M., Purcell, L., Putukian, M., Schneider, K., Tator, C., Turner, M., 2013. 

Consensus statement on Concussion in Sport--the 4th International Conference on Concussion in Sport held in Zurich, 

November 2012. J Sci Med Sport 16, 178-189.

• Meythaler, J.M., Peduzzi, J.D., Eleftheriou, E., Novack, T.A., 2001. Current concepts: diffuse axonal injury-associated 

traumatic brain injury. Arch Phys Med Rehabil 82, 1461-1471.

• Niogi, S.N., Mukherjee, P., 2010. Diffusion tensor imaging of mild traumatic brain injury. J Head Trauma Rehabil 25, 241-255.

• Okie, S., 2005. Traumatic brain injury in the war zone. N Engl J Med 352, 2043-2047.

• Patel, N.Y., Hoyt, D.B., Nakaji, P., Marshall, L., Holbrook, T., Coimbra, R., Winchell, R.J., Mikulaschek, A.W., 2000. Traumatic 

brain injury: patterns of failure of nonoperative management. J Trauma 48, 367-374; discussion 374-365.

• Peskind, E.R., Petrie, E.C., Cross, D.J., Pagulayan, K., McCraw, K., Hoff, D., Hart, K., Yu, C.E., Raskind, M.A., Cook, D.G., 

Minoshima, S., 2011. Cerebrocerebellar hypometabolism associated with repetitive blast exposure mild traumatic brain 

injury in 12 Iraq war Veterans with persistent post-concussive symptoms. Neuroimage 54 Suppl 1, S76-82.

• Povlishock, J.T., 1993. Pathobiology of traumatically induced axonal injury in animals and man. Ann Emerg Med 22, 980-986.
References/Suggested Reading 4

• Riecker, A., Wildgruber, D., Mathiak, K., Grodd, W., Ackermann, H., 2003. Parametric analysis of rate-dependent 

hemodynamic response functions of cortical and subcortical brain structures during auditorily cued finger tapping: a fMRI 

study. Neuroimage 18, 731-739.

• Ruff, R.M., Iverson, G.L., Barth, J.T., Bush, S.S., Broshek, D.K., Policy, N.A.N., Planning, C., 2009. Recommendations for 

diagnosing a mild traumatic brain injury: a National Academy of Neuropsychology education paper. Arch Clin Neuropsychol

24, 3-10.

• Saatman, K.E., Duhaime, A.C., Bullock, R., Maas, A.I., Valadka, A., Manley, G.T., Workshop Scientific, T., Advisory Panel, M., 

2008. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 25, 719-738.

• Taber, K.H., Warden, D.L., Hurley, R.A., 2006. Blast-related traumatic brain injury: what is known? J Neuropsychiatry Clin

Neurosci 18, 141-145.

• Teasdale, G., Jennett, B., 1974. Assessment of coma and impaired consciousness. A practical scale. Lancet 2, 81-84.

• Thurman, D.J., Alverson, C., Dunn, K.A., Guerrero, J., Sniezek, J.E., 1999. Traumatic brain injury in the United States: A public 

health perspective. J Head Trauma Rehabil 14, 602-615.

• Xiong, Y., Gu, Q., Peterson, P.L., Muizelaar, J.P., Lee, C.P., 1997. Mitochondrial dysfunction and calcium perturbation induced 

by traumatic brain injury. J Neurotrauma 14, 23-34.