The objective was to compare two neurophysiological variables in active amateur boxers with non-boxing sportsmen. 41 boxers and 27 controls were given psychometric tests: 34 boxers and 34 controls underwent technetium-99m hexamethylpropyleneamineoxime single photon emission computerised tomography (Tc-99m HMPAO SPECT) cerebral perfusion scans. The controls performed better at most aspects of the psychometric tests. Boxers who had fought fewer bouts had a tendency to perform better at psychometric tests than those boxers who had fought more bouts. Tc-99m HMPAO SPECT cerebral perfusion scanning showed that controls had less aberrations in cerebral perfusion than the boxers. In conclusion, significant differences were shown in two neurophysiological variables between young amateur sportsmen who box and those who do not. The long term effects of these findings remain unknown.
Due to the use of improvised explosive devices, blast exposure and mild traumatic brain injury (mTBI) have become hallmark injuries of the Iraq and Afghanistan wars. Although the mechanisms of the effects of blast on human neurobiology remain active areas of investigation, research suggests that the cerebrovasculature may be particularly vulnerable to blast via molecular processes that impact cerebral blood flow. Given that recent work suggests that blast exposure, even without a subsequent TBI, may have negative consequences on brain structure and function, the current study sought to further understand the effects of blast exposure on perfusion. One hundred and eighty military personnel underwent pseudo-continuous arterial spin labeling (pCASL) imaging and completed diagnostic and clinical interviews. Whole-brain analyses revealed that with an increasing number of total blast exposures, there was significantly increased perfusion in the right middle/superior frontal gyri, supramarginal gyrus, lateral occipital cortex, and posterior cingulate cortex as well as bilateral anterior cingulate cortex, insulae, middle/superior temporal gyri and occipital poles. Examination of other neurotrauma and clinical variables such as close-range blast exposures, mTBI, and PTSD yielded no significant effects. These results raise the possibility that perfusion may be an important neural marker of brain health in blast exposure.
Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used for measuring cerebral blood flow (CBF) in a completely non-ionizing and non invasive fashion. ASL is useful in perfusion studies on healthy adult & pediatric subjects, individuals who need multiple follow-ups, and patients with varying cerebrovascular diseases where changes in CBF can be used as an indicator of tissue viability. We used a variation of the ASL technique known as pseudo-continuous ASL (pCASL). This form of ASL is the clinical standard (Alsop et al., 2015). However, it is not well documented the that pCASL is reliable between sessions spanning days to weeks. In this study, we assessed the inter-session reliability of CBF through the use of the pCASL technique. We hypothesize that the pCASL technique can be used to quantify CBF measurements across a 24-hour and 48-hour period. Subjects included 15 healthy, active duty Air Force military personnel recruited by the Wright Patterson Air Force Base from a larger experiment. Of the 15 subjects scanned on day 1 and day 2, 2 did not return for scanning on the third day. All participants were scanned in three identical evening sessions separated by 24 hours. MR imaging was conducted on a 3T MRI scanner with a 24-channel head coil. Each of the three days began with a baseline imaging scan followed by sham transcranial direct current stimulation (tDCS) and another identical imaging session. MRI acquisition included a 12-min resting-state function MRI (fMRI), three task fMRI, a T1-weighted MRI, diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS) imaging, and resting pCASL. Our work only shows the baseline imaging from each day and the resting pCASL results. Quantitative CBF maps were computed from the raw pCASL data using proton density maps and a single compartment perfusion model through the use of the clinical processing pipeline on the MRI. These CBF maps were then registered to a reference space. Changes in CBF between the three pre-sham stimulation days were analyzed on a voxel-wise basis through a one-sample t-test and permutation testing using 215 (32,768) permutations for the difference between day 1 and day 2 and 213 (8192) permutations for the difference between day 1 and day 3 and day 2 and day 3. Permutation test results were not cluster-corrected for multiple comparisons to be conservative with respect to our hypothesis but were thresholded with a t-statistic of 2.3. The experiment's results indicated that the pCASL MRI technique can indeed be used reliably in radiological evaluation to quantitatively assess CBF within a 24-hour but not quite in a 48-hour periods.
Background: Neurobiologic studies have suggested that dysregulation of central noradrenergic systems may be involved in the pathophysiology of attention deficit hyperactivity disorder (ADHD), and it has been hypothesized that genetic changes in the norepinephrine pathways might contribute to dysfunction of the prefrontal cortex circuits in ADHD. We previously reported decreased cerebral blood flow in the right lateral prefrontal cortex and both orbitofrontal cortices in children with ADHD. Genetic investigations have shown that the alpha-2A-adrenergic receptor gene (ADRA2A) is associated with ADHD. Our aim was to examine whether the presence of a risk allele of the ADRA2A MspI polymorphism is associated with differences in regional cerebral blood flow in boys with ADHD. Methods: We recruited 21 Korean boys with ADHD (mean age 9.9, standard deviation [SD] 2.7 yr) and 11 age-and sex-matched controls (mean age 10.6 [SD 2.1] yr). Each participant underwent technetium-99m-hexamethylpropylene amine oxime ((99m)Tc-HMPAO) single-photon emission computed tomography. We performed image analyses with voxel-wise t statistics using SPM2. Results: We found regional hypoperfusion in the prefrontal regions, including the right orbitofrontal and right medial gyri, and the bilateral putamen and cerebellum in boys with ADHD relative to controls (p < 0.0005, uncorrected for multiple comparisons). Boys with ADHD who carried the C allele (n = 13) at the ADRA2A MspI polymorphism had reduced perfusion in the bilateral orbitofrontal regions compared with those without the C allele (n = 8) (p < 0.0005, uncorrected for multiple comparisons). Limitations: This study was limited by the small sample size, and we did not obtain genetic data from the controls. Conclusion: Our findings suggest that regional differences in cerebral perfusion in the orbitofrontal cortex represent an intermediate neuroimaging phenotype associated with the ADRA2A MspI polymorphism; these data support the validity of the noradrenergic hypothesis regarding the pathophysiology of ADHD. ; This work was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF- 2006–003-E00192). ; Varghese GI, 2009, BRAIN, V132, P2102, DOI 10.1093/brain/awp027 ; May A, 2009, NAT REV NEUROL, V5, P199, DOI 10.1038/nrneurol.2009.28 ; Makris N, 2009, DEV NEUROSCI-BASEL, V31, P36, DOI 10.1159/000207492 ; Cho SC, 2008, AM J MED GENET B, V147B, P957, DOI 10.1002/ajmg.b.30725 ; Durston S, 2008, DEV PSYCHOPATHOL, V20, P1133, DOI 10.1017/S0954579408000539 ; Prince J, 2008, J CLIN PSYCHOPHARM, V28, pS39, DOI 10.1097/JCP.0b013e318174f92a ; Brennan AR, 2008, ANN NY ACAD SCI, V1129, P236, DOI 10.1196/annals.1417.007 ; Wang M, 2007, CELL, V129, P397, DOI 10.1016/j.cell.2007.03.015 ; Arnsten AFT, 2006, NEUROPSYCHOPHARMACOL, V31, P2376, DOI 10.1038/sj.npp.1301164 ; Dickstein SG, 2006, J CHILD PSYCHOL PSYC, V47, P1051, DOI 10.1111/j.1469-7610.2006.01671.x ; Krain AL, 2006, CLIN PSYCHOL REV, V26, P433, DOI 10.1016/j.cpr.2006.01.005 ; Wang B, 2006, AM J MED GENET B, V141B, P130, DOI 10.1002/ajmg.b.30258 ; Waldman ID, 2006, COGN AFFECT BEHAV NE, V6, P18 ; Biederman J, 2005, LANCET, V366, P237 ; Bush G, 2005, BIOL PSYCHIAT, V57, P1273, DOI 10.1016/j.biopsych.2005.01.034 ; Madras BK, 2005, BIOL PSYCHIAT, V57, P1397, DOI 10.1016/j.biopsych.2004.10.011 ; Park L, 2005, MOL PSYCHIATR, V10, P572, DOI 10.1038/sj.mp.4001605 ; Sawyer SL, 2005, EUR J HUM GENET, V13, P677, DOI 10.1038/sj.ejhg.5201368 ; Lee JS, 2005, HUM BRAIN MAPP, V24, P157, DOI 10.1002/hbm.20067 ; Bobb AJ, 2005, AM J MED GENET B, V132B, P109, DOI 10.1002/ajmg.b.30086 ; Szobot C, 2005, AM J MED GENET B, V132B, P53, DOI 10.1002/ajmg.b.30096 ; Belfer I, 2005, J HUM GENET, V50, P12, DOI 10.1007/s10038-004-0211-y ; Kim YS, 2004, YONSEI MED J, V45, P81 ; Kim BN, 2002, EUR ARCH PSY CLIN N, V252, P219, DOI 10.1007/s00406-002-0384-3 ; PARK KS, 2002, KOREAN ED DEV I WECH ; Peyron R, 2000, NEUROPHYSIOL CLIN, V30, P263 ; Avery RA, 2000, NEUROPSYCHOPHARMACOL, V23, P240 ; Mao ZM, 1999, BIOL PSYCHIAT, V46, P1259 ; Jakala P, 1999, NEUROPSYCHOPHARMACOL, V20, P460 ; Berquin PC, 1998, NEUROLOGY, V50, P1087 ; May A, 1998, PAIN, V74, P61 ; Kaufman J, 1997, J AM ACAD CHILD PSY, V36, P980 ; Smalley SL, 1997, AM J HUM GENET, V60, P1276 ; Allen G, 1997, SCIENCE, V275, P1940 ; Lario S, 1997, CLIN GENET, V51, P129 ; AMEN DG, 1997, ANN CLIN PSYCHIAT, V9, P81 ; Arnsten AFT, 1996, ARCH GEN PSYCHIAT, V53, P448 ; HARVEY AS, 1993, EPILEPSIA, V34, P869 ; ZAMETKIN AJ, 1993, ARCH GEN PSYCHIAT, V50, P333 ; ARNSTEN AFT, 1988, J NEUROSCI, V8, P4287 ; HOEHE MR, 1988, NUCLEIC ACIDS RES, V16, P9070 ; TALAIRACH J, 1988, COPLANAR STEREOTAXIC ; CHANG LT, 1978, IEEE T NUCL SCI, V25, P638 ; 1
Background: Delayed cerebral ischemia (DCI) is usually caused by cerebral vasospasm (CVS). To detect DCI and CVS a cranial CT scan will be performed, but cervical vessels are not necessarily displayed.
Patient: A 63-year-old female patient who suffered from aneurysmal subarachnoid hemorrhage (SAH) was treated at the authors' institution. After an initially unremarkable clinical course, she developed aphasia on day 11. CT angiography (CTA) and perfusion imaging revealed significant hypoperfusion of the left hemisphere. In addition, the CTA showed a subtotal stenosis of the internal carotid artery (ICA) at the level of the petrous segment, suspicious for a dissection. This was not detectable angiographically in the final control of the intervention and was also not clinically evident until day 11. Cerebral perfusion as well as the clinical symptoms normalized rapidly after stent reconstruction of the ICA.
Conclusion: Even though CVS is the most frequent cause of hypoperfusion in patients after SAH, a periinterventional dissection can also lead to relevant stenosis and thus to a disturbed cerebral perfusion and corresponding neurological deficits. The time delay between the intervention and the clinical as well as CT-angiographical manifestation in our case is remarkable.
Background Although type 2 diabetes mellitus (T2DM) is an established risk factor for cognitive impairment, the underlying mechanisms remain poorly explored. One potential mechanism may be through effects of T2DM on cerebral perfusion. The current study hypothesized that T2DM is associated with altered peripheral and central hemodynamic responses to orthostasis, which may in turn be associated with cognitive impairment in T2DM.
Methods A novel use of function-on-scalar regression, which allows the entire hemodynamic response curve to be modeled, was employed to assess the association between T2DM and hemodynamic responses to orthostasis. Logistic regression was used to assess the relationship between tissue saturation index (TSI), T2DM, and cognitive impairment. All analyses used cross-sectional data from Wave 3 of The Irish Longitudinal Study on Ageing (TILDA).
Results Of 2 984 older adults (aged 64.3 ± 8.0; 55% female), 189 (6.3%) had T2DM. T2DM was associated with many features that are indicative of autonomic dysfunction including a blunted peak heart rate and lower diastolic blood pressure. T2DM was associated with reduced TSI and also with greater odds of impaired performance on the Montreal Cognitive Assessment (odds ratio [OR]: 1.62; confidence interval [CI: 1.07, 2.56]; p = .019). Greater TSI was associated with lower odds of impaired performance (OR: 0.90, CI [0.81–0.99]; p = .047).
Conclusions T2DM was associated with impaired peripheral and cerebral hemodynamic responses to active stand. Both T2DM and reduced cerebral perfusion were associated with impaired cognitive performance. Altered cerebral perfusion may represent an important mechanism linking T2DM and adverse brain health outcomes in older adults.
AbstractTranscriptomics, regional cerebral blood flow (rCBF), and a virtual reality-based spatial motor task were integrated using mediation analysis in a novel demonstration of "imaging omics." Data collected in National Collegiate Athletic Association (NCAA) Division I football athletes cleared for play before in-season training showed significant relationships in 1) elevated levels of miR-30d and miR-92a to elevated putamen rCBF, 2) elevated putamen rCBF to compromised Balance scores, and 3) compromised Balance scores to elevated microRNA (miRNA) levels. rCBF acted as a consistent mediator variable (Sobel's test P < 0.05) between abnormal miRNA levels and compromised Balance scores. Given the involvement of these miRNAs in inflammation and immune function and that vascular perfusion is a component of the inflammatory response, these findings support a chronic inflammatory model in these athletes with 11 years of average football exposure. rCBF, a systems biology measure, was necessary for miRNA to affect behavior.
Fragestellung: Die time varying elastance, der Gold-Standart zur Bestimmung der myokardialen Kontraktilität, kann entweder mittels Druck-Volumen Kurven, die mit einem Conductance-Katheter gemessen wurden, oder über eine, mittels Ultraschalltechnik generierte, Fluß-Flächen-Beziehung bestimmt werden. Letztere könnte durch Vasomotion beeinflusst werden, da hier die Blutfluß-Beschleunigung in der Arteria carotis gemessen wird. So ist es Ziel dieser Arbeit den störenden Einfuß von Eigenschaften des Gefäßsystems auf einen myokardialen Kontraktilitätsparameter zu untersuchen. Methodik: Nach der Versuchsgenehmigung durch die Regierung von Unerfranken wurden 9 Merino- Schafe narkotisiert und es wurden hämodynamische Messsungen durchgeführt (MAD, HF, ZVD, HZV). Die time varying elastance wurde sowohl mittels Conductance-Katheter (Ees), als auch über die ultraschallgestützte Fluß-Flächen-Beziehung (E´es) bestimmt. Nach einer Trepanation wurden zwei Sonden zur Messung der zerebralen Gewebsoxygenierung (P(ti)O2) und der Stoffwechselmetabolite (Laktat, Pyruvat, L/P-Verhältnis) mittels Mikrodialyse subkortikal ins Hirngewebe eingeführt. Die zerebrale Perfusion wurde mittels Laser- Doppler überwacht. Studienprotokoll: Die hämodynamischen Messungen (inklusive Ees und E´es), P(ti)O2, Laktat, Pyruvat und L/P wurden unter Ausgangsbedingungen (baseline1), unter dem Einfluß von Nitroprussidnatrium (NPN) , nach Rückkehr zu Ausgangsbedingungen (baseline 2) und unter dem Einfluß von Esmolol (Esmolol) durchgeführt. Sowohl unter NPN, als auch unter Esmolol wurde ein MAD von 50 mmHg für 15 min aufrechterhalten. Ebenso wurde für die Messungen unter baseline ein MAD von 90 mmHg für 15 min aufrechterhalten. Ergebnisse: Neun Schafe (63 ± 4 kg) wurden der weiteren Analyse zugeführt. Die Mikrodialyse konnte in zwei Fällen nicht durchgeführt werden. Der MAD fiel, wie angestrebt, sowohl unter NPN (50±11 mmHg), als auch unter Esmolol (48±6 mmHg) verglichen mit den Ausgangsbedingungen (baseline 1 (90±21 mmHg); baseline 2 (90±16 mmHg). Die HF unter Esmolol (73±14 min-1) unterschied sich signifikant von baseline 1 (90±21 min-1), baseline 2 (81±23 min-1) und NPN (94±23 min-1). Die Ees fiel signifikant unter Esmolol (1,0±0,2 mmHg * cm-3) verglichen mit baseline 1 (3,0±0,9 mmHg * cm-3), baseline 2 (3,2±0,8 mmHg * cm-3) und NPN (3,0±0,7 mmHg * cm-3). Die Ees fiel ebenfalls signifikant ab unter Esmolol (0,36±0,21 sec-1 * cm-1), verglichen mit baseline 1 (0,88±0,26 sec-1 * cm-1), baseline 2 (0,89±0,24 sec-1 * cm-1) und NPN (0,76±0,27 sec-1 * cm-1). Das HZV sank signifikant in Folge Esmolol-Gabe verglichen mit Ausgangsbedingungen (2,4±1,0 ml * min-1 baseline 1 und baseline 2) und NPN (3,2±2,0 ml * min-1). Im Laser- Doppler zeigte sich ein Abfall der zerebralen Perfusion unter NPN und Esmolol, wobei dieser Abfall unter Esmolol signifikant größer war als unter NPN. In 7 Fällen wurde das L/P- Verhältnis mittels Mikrodialyse bestimmt. Hier konnte ein signifikanter Anstieg unter Esmolol, verglichen mit baseline 1, baseline 2 und NPN, gesehen werden. Für die P(ti)O2 konnte ein Abfall von um die 50% unter Esmolol beobachtet werden, verglichen mit baseline 1, baseline 2 und NPN. In der linearen Regressionsanalyse konnte eine gute Korrelation von Ees und E´es (Ees = 1,4 * E´es + 1,5; R= 0,90, R2= 0,81; p < 0,0001) gezeigt werden. Sowohl zur Regressionanalyse von P(ti)O2 und L/P-Verhältnis, als auch von E´es und Ees wurden die Daten von 7 Tieren verwendet. P(ti)O2 und L/P-Verhältnis korrelierten am besten in Form einer Exonentialfunktion: P(ti)O2=63,3L/P-0,5;(R=0,82, R2=0,67 und p<0,0001). P(ti)O2 und Ees korrelierten am besten in Form einer Linearfunktion: P(ti)O2=22,2 Ees*0,8; (R=0,58,R2=0,34, und p<0,001). Auch P(ti)O2 und E´es korrelierten am besten in Form einer Linearfunktion: P(ti)O2=44,0 E´es-3,8; (R=0,64,R2=0,4, und p<0,001). Die Daten von 7 Tieren wurden einer multiplen linearen Regressionanalyse zugeführt (P(ti)O2 gegen Kontraktilität (hier nur Ees, um Multikolinearität zu vermeiden), MAD, HF, HZV und ZVD). Diesem Ergebnis folgend (P(ti)O2= 13+(7*Ees)+(0,1*MAD)+(2*ZVD)-(0,04*HF)+(0,004*HZV); R=0,88, R2=0,77, und p<0,001) scheint das HZV der hämodynamische Parameter zu sein, der den größten Einfluß auf die P(ti)O2 hat. Schlussfolgerung: Die Ergebnisse sprechen dagegen, dass Vasomotion einen störenden Einfluß auf die ultraschallgestützte myokardiale Kontraktilitätsbestimmung hat. Dass das HZV von allen hier gemessenen hämodynamischen Parametern den größten Einfluß auf die Sauerstoffsättigung des Hirngewebes hat, scheint nicht weiter überraschend. Im klinischen Alltag jedoch wird immer noch, gerade bei Patienten mit gestörter zerebraler Perfusion zumeist auf den MAD vertraut. Hier scheint weitere Forschung angezeigt. ; Objective: Time varying elastance, the gold-standart for measuring myocardial contractility, can be determined either by processing conductance-catheter derived pressure-volume loops or by processing ultrasound derived velocity-area loops. The latter might be influenced by vasomotion, as the flow-velocity is measured in the carotid artery. So properties of the arterial vascular system, such as cerebral autoregulation, might have a disturbing influence on the measurement of myocardial contractility. The investigation of this influence is objective of this study. Methods: With permission of the Committee for Laboratory Animal Care 9 Merino- sheep were anesthetized. Hemodynamic measurement was performed (MABP, HR, CVP, CO). Time varying elastance was determined either by conductance-catheter derived pressure-volume loops (Ees) or by ultrasound derived velocity-area loops (E´es). After trepanation two probes for measuring cerebral tissue oxygenation (P(ti)O2) and the metabolic markers (Lactate, Pyruvate, L/P) via microdialysis were inserted subcortical into the brain tissue. Cerebral perfusion was controlled by Laser- Doppler Flowmetry. Protocol: Hemodynamic measurements (including Ees and E´es), P(ti)O2, Lactate, Pyruvate and L/P were performed during baseline conditions (baseline1), during conditions due to Sodium Nitroprusside (SNP) mediated afterload reduction, after the return to baseline conditions (baseline 2) and during a period of reduced myocardial conractility after the administration of Esmolol (Esmolol). As well during the SNP as during the Esmolol period MABP was of the order of 50 mmHg for 15 min. For 15 min as well a MABP of 90 mmHg was maintained constant in the course of baseline conditions. Results: Nine sheep (63 ± 4 kg) were analysed. Microdialysis couldn´t be performed in two cases. MABP dropped either during SNP (50±11 mmHg) or during Esmolol (48±6 mmHg) infusion, compared to baseline (baseline 1 (90±21 mmHg); baseline 2 (90±16 mmHg). HR during Esmolol (73±14 min-1) was significantly different compared to baseline 1 (90±21 min-1), baseline 2 (81±23 min-1) and SNP (94±23 min-1). Ees dropped significantly during Esmolol (1,0±0,2 mmHg * cm-3) compared to baseline 1 (3,0±0,9 mmHg * cm-3), baseline 2 (3,2±0,8 mmHg * cm-3) and SNP (3,0±0,7 mmHg * cm-3). Ees as well dropped significantly during Esmolol (0,36±0,21 sec-1 * cm-1), compared to baseline 1 (0,88±0,26 sec-1 * cm-1), baseline 2 (0,89±0,24 sec-1 * cm-1) and SNP (0,76±0,27 sec-1 * cm-1). CO dropped significantly following the application of Esmolol compared to baseline (2,4±1,0 ml * min-1 baseline 1 and baseline 2) and SNP (3,2±2,0 ml * min-1). Cerebral perfusion, measured by Laser- Doppler Flowmetry was reduced during SNP and Esmolol, though the reduction during Esmolol was significantly greater than during SNP. L/P- ratio via microdialysis was determined in 7 cases, where an significant increase could be observed during Esmolol compared to baseline 1, baseline 2 and SNP. For P(ti)O2 a decrease in the order of 50% could be observed during Esmolol compared to baseline 1, baseline 2 and SNP. Good correlation via linear regression analysis could be found for Ees and E´es (Ees = 1,4 * E´es + 1,5; R= 0,90, R2= 0,81; p < 0,0001). For regressionanalysis between P(ti)O2 and L/P-ratio, as well as between E´es und Ees data of 7 animals were used. Best correlation in the case of P(ti)O2 and L/P-ratio was found for an exponential function: P(ti)O2=63,3L/P-0,5;(R=0,82, R2=0,67 and p<0,0001). In the case of P(ti)O2 und Ees best correlation was found for a linear function: P(ti)O2=22,2 Ees*0,8; (R=0,58,R2=0,34, and p<0,001). For correlation between P(ti)O2 and E´es a linear function was found: P(ti)O2=44,0 E´es-3,8; (R=0,64,R2=0,4, and p<0,001). The data of 7 animals were used for multiple linear regressionanalysis (P(ti)O2 vs. contractility (just Ees, to avoid multicolinearity), MABP, HR, CO and CVP). According to this correlation (P(ti)O2= 13+(7*Ees)+(0,1*MABP)+(2*CVP)-(0,04*HR)+(0,004*CO); R=0,88, R2=0,77, and p<0,001) CO seems to be the cardiovascular parameter that has an significant influence on P(ti)O2. Conclusions: Our data strongly suggest that the determination of myocardial contractility via ultrasound derived velocity-area loops is not relevantly influenced by vasomotion. The finding that CO has the strongest effect on cerebral tissue oxygenation amongst all the measured hemodynamic parameters is not very surprising, but in patients with disturbed cerebral perfusion most clinicians still rely on MABP. Obviously this has to be investigated further.