Clinical utility of SPECT neuroimaging in the diagnosis and treatment of traumatic brain injury: a systematic review.

PURPOSE: This systematic review evaluated the clinical utility of single photon emission computed tomography (SPECT) in traumatic brain injury (TBI). METHODS: After defining a PICO Statement (Population, Intervention, Comparison and Outcome Statement), PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were applied to identify 1600 articles. After screening, 374 articles were eligible for review. Inclusion for review was focus on SPECT in the setting of mild, moderate, or severe TBI with cerebral lobar specificity of SPECT findings. Other inclusion criteria were comparison modalities in the same subjects and articles in English. Foreign language articles, SPECT studies that did not include comparison modalities, and case reports were not included for review. RESULTS: We identified 19 longitudinal and 52 cross-sectional studies meeting inclusion criteria. Three longitudinal studies examined diagnostic predictive value. The first showed positive predictive value increases from initial SPECT scan shortly after trauma to one year follow up scans, from 59% to 95%. Subsequent work replicated these results in a larger cohort. Longitudinal and cross sectional studies demonstrated SPECT lesion localization not detected by CT or MRI. The most commonly abnormal regions revealed by SPECT in cross-sectional studies were frontal (94%) and temporal (77%) lobes. SPECT was found to outperform both CT and MRI in both acute and chronic imaging of TBI, particularly mild TBI. It was also found to have a near 100% negative predictive value. CONCLUSIONS: This review demonstrates Level IIA evidence (at least one non-randomized controlled trial) for the value of SPECT in TBI. Given its advantages over CT and MRI in the detection of mild TBI in numerous studies of adequate quality, and given its excellent negative predictive value, it may be an important second test in settings where CT or MRI are negative after a closed head injury with post-injury neurological or psychiatric symptoms.

Multi-site six month outcome study of complex psychiatric patients evaluated with addition of brain SPECT imaging.

BACKGROUND: Psychiatric diagnoses are made primarily through clinical histories, with psychiatrists searching for DSM (Diagnostic and Statistical Manual of Mental Disorders)-driven symptom clusters, and outcomes for patients have not substantially improved in decades for many disorders. PRIMARY STUDY OBJECTIVE: In this study, the research team examined the outcome impact of the addition of single photon emission computed tomography (SPECT) to the assessment of complex patients. DESIGN: The research team designed a multisite, prospective, 6-mo outcome study. The study was completed after final outcome measures were obtained on 500 participants. SETTING: The study occurred in four psychiatric clinics, the Amen Clinics in Newport Beach and San Francisco, CA; Bellevue, WA; and Reston, VA. PARTICIPANTS: Participants were new outpatients at the four clinics who were entered into the study between January 2011 and August 2012. PRIMARY OUTCOME MEASURES: Evaluations included (1) histories, (2) mental-status examinations, (3) a Structured Clinical Interview for DSM-IV (SCID-IV), (4) the Beck Depression Inventory-II (BDI-II), (5) the Brief Symptom Inventory (BSI), (6) the Quality of Life Inventory (QOLI), and (7) brain SPECT scans during rest and concentration. At 6 mo, standardized outcome measurements were readministered (BDI-II, BSI, QOLI), and the research team asked questions about improvement and compliance. RESULTS: Seventy-five percent of participants reported significant clinical improvement; 55% reported being "very compliant," 41% "somewhat compliant," and 4% "noncompliant." Significant improvements were observed across all three assessments: (1) BDI, 360 out of 500 (72%) participants decreased, mean difference=-6.92; (2) BSI, 367 out of 461 (80%) participants decreased, mean difference=-0.39.; (3) QOLI, 427 (85%) of participants improved) at 6 mo (Hotelling T2=460; P<.0001), mean difference=+1.65. Net improvement was measured at 81% (n=405). CONCLUSIONS: To the research team's knowledge, this study is the first outcome study of complex psychiatric patients using SPECT as an additional diagnostic tool and demonstrating significant improvement. Further studies comparing the addition of brain SPECT to "treatment as usual" groups are warranted.

Effects of brain-directed nutrients on cerebral blood flow and neuropsychological testing: a randomized, double-blind, placebo-controlled, crossover trial.

CONTEXT: In a prior open trial of professional football players who displayed the effects of traumatic brain injury, the current reserach team reported significant improvements in clinical symptoms, neuropsychological testing and regional cerebral blood flow (rCBF) following the use of brain-directed nutrients (BDNs) and lifestyle interventions. OBJECTIVE: The current study intended to determine whether supplementation with BDNs improved rCBF and neuropsychological function in healthy individuals. DESIGN: The current study was a randomized, doubleblind, placebo-controlled, crossover trial, which was a more rigorous reseach design than the prior study and did not include lifestyle interventions. SETTING: Participants underwent evaluation and testing at the Amen Clinics, Inc, a private medical facility in Newport Beach, CA. PARTICIPANTS: Thirty healthy adult (15 male and 15 female) participants were recruited from the community though local advertising and met the requirements for eligibility into the study. Twenty-five individuals completed the study, with dropout due to events unrelated to the study itself. INTERVENTION: The participants were randomly assigned to a treatment order for intervention, either placebo or brain supplements first. The BDNs treatment was comprised of three supplements: fish oil; a high-potency, multiple vitamin/mineral supplement; and a brainenhancement supplement. The placebo treatment was two supplements comprised of rice flour to replace the multiple vitamin/mineral complex and the brain-enhancement supplement and one supplement made of other oils to replace the fish-oil mixture. After 2 mo of this first intervention, a crossover intervention occurred for a final 2 mo, in which participants formerly receiving BDNs received a placebo treatment and participants formerly treated with placebo received the BDNs treatment. OUTCOME MEASURES: Primary outcome measures included (1) an analysis of the changes in rCBF using SPECT and (2) an assessment of the differences in cognitive and emotional function using the MicroCog (cognitive performance), the WebNeuro (emotional state), and three psychological inventories-the Beck Depression Inventory (BDI-II), Brief Symptom Inventory (BSI), and Quality of Life Inventory (QOLI). RESULTS: A region of interest (ROI) analysis for each of the 2-mo phases (baseline, then placebo and treatment according to randomized order) showed significant improvement in rCBF for the BDNs as compared to the placebo (as assigned at the start of the first intervention) in the prefrontal cortex, anterior and posterior cingulate gyrus, hippocampus, and cerebellum. Significant improvements were observed for the BDNs (1) on the MicroCog-reasoning, P=.008; memory, P=.014; information processing accuracy, P=.027; (2) on the WebNeuro-executive function, P=.002, information processing efficiency, P=.015; depressed mood, P=.017, and emotional identification, P=.041; and (3) on the BSI-positive symptom total, P=.024 and reduced hostility, P=.018. For the last, significance occurred upon accounting for the effect of order. CONCLUSION: This study demonstrates the potential effectiveness of BDNs in enhancing rCBF and neuropsychological function across various cognitive and psychological domains.

A phase I study of low-pressure hyperbaric oxygen therapy for blast-induced post-concussion syndrome and post-traumatic stress disorder.

This is a preliminary report on the safety and efficacy of 1.5 ATA hyperbaric oxygen therapy (HBOT) in military subjects with chronic blast-induced mild to moderate traumatic brain injury (TBI)/post-concussion syndrome (PCS) and post-traumatic stress disorder (PTSD). Sixteen military subjects received 40 1.5 ATA/60 min HBOT sessions in 30 days. Symptoms, physical and neurological exams, SPECT brain imaging, and neuropsychological and psychological testing were completed before and within 1 week after treatment. Subjects experienced reversible middle ear barotrauma (5), transient deterioration in symptoms (4), and reversible bronchospasm (1); one subject withdrew. Post-treatment testing demonstrated significant improvement in: symptoms, neurological exam, full-scale IQ (+14.8 points; p<0.001), WMS IV Delayed Memory (p=0.026), WMS-IV Working Memory (p=0.003), Stroop Test (p<0.001), TOVA Impulsivity (p=0.041), TOVA Variability (p=0.045), Grooved Pegboard (p=0.028), PCS symptoms (Rivermead PCSQ: p=0.0002), PTSD symptoms (PCL-M: p<0.001), depression (PHQ-9: p<0.001), anxiety (GAD-7: p=0.007), quality of life (MPQoL: p=0.003), and self-report of percent of normal (p<0.001), SPECT coefficient of variation in all white matter and some gray matter ROIs after the first HBOT, and in half of white matter ROIs after 40 HBOT sessions, and SPECT statistical parametric mapping analysis (diffuse improvements in regional cerebral blood flow after 1 and 40 HBOT sessions). Forty 1.5 ATA HBOT sessions in 1 month was safe in a military cohort with chronic blast-induced PCS and PTSD. Significant improvements occurred in symptoms, abnormal physical exam findings, cognitive testing, and quality-of-life measurements, with concomitant significant improvements in SPECT.

Reversing brain damage in former NFL players: implications for traumatic brain injury and substance abuse rehabilitation.

Brain injuries are common in professional American football players. Finding effective rehabilitation strategies can have widespread implications not only for retired players but also for patients with traumatic brain injury and substance abuse problems. An open label pragmatic clinical intervention was conducted in an outpatient neuropsychiatric clinic with 30 retired NFL players who demonstrated brain damage and cognitive impairment. The study included weight loss (if appropriate); fish oil (5.6 grams a day); a high-potency multiple vitamin; and a formulated brain enhancement supplement that included nutrients to enhance blood flow (ginkgo and vinpocetine), acetylcholine (acetyl-l-carnitine and huperzine A), and antioxidant activity (alpha-lipoic acid and n-acetyl-cysteine). The trial average was six months. Outcome measures were Microcog Assessment of Cognitive Functioning and brain SPECT imaging. In the retest situation, corrected for practice effect, there were statistically significant increases in scores of attention, memory, reasoning, information processing speed and accuracy on the Microcog. The brain SPECT scans, as a group, showed increased brain perfusion, especially in the prefrontal cortex, parietal lobes, occipital lobes, anterior cingulate gyrus and cerebellum. This study demonstrates that cognitive and cerebral blood flow improvements are possible in this group with multiple interventions.

Cerebral blood flow differences between long-term meditators and non-meditators.

We have studied a number of long-term meditators in previous studies. The purpose of this study was to determine if there are differences in baseline brain function of experienced meditators compared to non-meditators. All subjects were recruited as part of an ongoing study of different meditation practices. We evaluated 12 advanced meditators and 14 non-meditators with cerebral blood flow (CBF) SPECT imaging at rest. Images were analyzed with both region of interest and statistical parametric mapping. The CBF of long-term meditators was significantly higher (p<.05) compared to non-meditators in the prefrontal cortex, parietal cortex, thalamus, putamen, caudate, and midbrain. There was also a significant difference in the thalamic laterality with long-term meditators having greater asymmetry. The observed changes associated with long-term meditation appear in structures that underlie the attention network and also those that relate to emotion and autonomic function.

Cerebral blood flow changes during chanting meditation.

PURPOSE: To examine changes in brain physiology during a chanting meditation practice using cerebral blood flow single-photon emission computed tomography. METHODS: Single-photon emission computed tomography scans were acquired in 11 healthy individuals during either a resting state or meditation practice randomly performed on two separate days. Statistical parametric mapping analyses were conducted to identify significant changes in regional cerebral blood flow (rCBF) between the two conditions. RESULTS: When the meditation state was compared with the baseline condition, significant rCBF increases were observed in the right temporal lobe and posterior cingulate gyrus, and significant rCBF decreases were observed in the left parietotemporal and occipital gyri. CONCLUSION: The results offer evidence that this form of meditation practice is associated with changes in brain function in a way that is consistent with earlier studies of related types of meditation as well as with the positive clinical outcomes anecdotally reported by its users.

High-resolution brain SPECT imaging and eye movement desensitization and reprocessing in police officers with PTSD.

Eye movement desensitization and reprocessing (EMDR) has been shown to be an effective treatment for posttraumatic stress disorder (PTSD). In this study, the authors evaluated the effectiveness and physiological effects of EMDR in police officers involved with on-duty shootings and who had PTSD. Six police officers involved with on-duty shootings and subsequent delayed-onset PTSD were evaluated with standard measures, the Posttraumatic Stress Diagnostic Scale, and high-resolution brain single photon emission computed tomography (SPECT) imaging before and after treatment. All police officers showed clinical improvement and marked reductions in the Posttraumatic Stress Diagnostic Scale Score (PDS). In addition, there were decreases in the left and right occipital lobe, left parietal lobe, and right precentral frontal lobe as well as significant increased perfusion in the left inferior frontal gyrus. In our study EMDR was an effective treatment for PTSD in this police officer group, showing both clinical and brain imaging changes.