P.185 Impact-detecting helmets as indicators of concussion and blood
                        brain barrier integrity in university football players

Background: Repetitive sub-concussive head impacts have been associated with changes in brain architecture and neurological symptoms. In this study, we examined the association between repetitive sub-concussive impacts, impact burden, and blood brain barrier (BBB) integrity in university football players. Methods: 59 university football players were followed over the 2019 season. Athletes with diagnosed concussion and those sustaining impacts that alerted a sideline impact monitor (relayed by ferroelectric helmet sensors) underwent dynamic contrast-enhanced MRI (DCE-MRI) within one week of injury/alert, and 4 weeks following initial incident. Results: Helmets recorded 2648 impacts over 48 cumulative hours. 8 concussions occurred during the 2019 season (2.82 per 1000 activity hours). On average, athletes with a diagnosed concussion had 55.3 impacts to the front sensor, compared to 14.1 in non-concussed athletes. Athletes who consented to DCE-MRI (n=5) had 10.78% BBB-D within a week of concussion/alert, and 6.77% BBB-D at 4-weeks. Conclusions: We show quantification of BBB integrity relative to head impact burden for the first time. This preliminary study highlights the potential of impact-detecting helmets to provide relevant impact characteristics and offers a foundation for future work on neurological consequences of repetitive sub-concussive impacts.

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Permeability of the windows of the brain: feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

Fluids and Barriers of the CNS ◽

10.1186/s12987-020-00228-x ◽

2020 ◽

Vol 17 (1) ◽

Author(s):

Inge C. M. Verheggen ◽

Joost J. A. de Jong ◽

Martin P. J. van Boxtel ◽

Alida A. Postma ◽

Frans R. J. Verhey ◽

...

Keyword(s):

Blood Brain Barrier ◽

Gray Matter ◽

Circumventricular Organs ◽

Brain Barrier ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Contrast Enhanced ◽

The Brain

Abstract Background Circumventricular organs (CVOs) are small structures without a blood–brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood–brain barrier absence. Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter. Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter. Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures. Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

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Permeability of the windows of the brain: Feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

10.21203/rs.3.rs-46100/v3 ◽

2020 ◽

Author(s):

Inge C.M. Verheggen ◽

Joost J.A. de Jong ◽

Martin P.J. van Boxtel ◽

Alida A. Postma ◽

Frans R.J. Verhey ◽

...

Keyword(s):

Blood Brain Barrier ◽

Gray Matter ◽

Circumventricular Organs ◽

Brain Barrier ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Contrast Enhanced ◽

The Brain

Abstract Background: Circumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence.Methods: Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter.Results: In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter.Conclusions: Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registration: Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

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Permeability of the windows of the brain: Feasibility of dynamic contrast-enhanced MRI of the circumventricular organs

10.21203/rs.3.rs-46100/v2 ◽

2020 ◽

Author(s):

Inge C.M. Verheggen ◽

Joost J.A. de Jong ◽

Martin P.J. van Boxtel ◽

Alida A. Postma ◽

Frans R.J. Verhey ◽

...

Keyword(s):

Blood Brain Barrier ◽

Gray Matter ◽

Circumventricular Organs ◽

Brain Barrier ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Contrast Enhanced ◽

The Brain

Abstract Background Circumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence.Methods Twenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter.Results In both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter.Conclusions Current measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registration Netherlands Trial Register number: NL6358, date of registration: 2017-03-24

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Permeability of the Windows of the Brain: Feasibility of Dynamic Contrast-enhanced MRI of the Circumventricular Organs

10.21203/rs.3.rs-46100/v1 ◽

2020 ◽

Author(s):

Inge C.M. Verheggen ◽

Joost J.A. de Jong ◽

Martin P.J. van Boxtel ◽

Alida A. Postma ◽

Frans R.J. Verhey ◽

...

Keyword(s):

Blood Brain Barrier ◽

Gray Matter ◽

Circumventricular Organs ◽

Brain Barrier ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Contrast Enhanced ◽

The Brain

Abstract BackgroundCircumventricular organs (CVOs) are small structures without a blood-brain barrier surrounding the brain ventricles that serve homeostasic functions and facilitate communication between the blood, cerebrospinal fluid and brain. Secretory CVOs release peptides and sensory CVOs regulate signal transmission. However, pathogens may enter the brain through the CVOs and trigger neuroinflammation and neurodegeneration. We investigated the feasibility of dynamic contrast-enhanced (DCE) MRI to assess the CVO permeability characteristics in vivo, and expected significant contrast uptake in these regions, due to blood-brain barrier absence.MethodsTwenty healthy, middle-aged to older males underwent brain DCE MRI. Pharmacokinetic modeling was applied to contrast concentration time-courses of CVOs, and in reference to white and gray matter. We investigated whether a significant and positive transfer from blood to brain could be measured in the CVOs, and whether this differed between secretory and sensory CVOs or from normal-appearing brain matter.ResultsIn both the secretory and sensory CVOs, the transfer constants were significantly positive, and all secretory CVOs had significantly higher transfer rates than each sensory CVO. The transfer constants in both the secretory and sensory CVOs were higher than in the white and gray matter.ConclusionsCurrent measurements confirm the often-held assumption of highly permeable CVOs, of which the secretory types have the strongest blood-to-brain transfer. The current study suggests that DCE MRI could be a promising technique to further assess the function of the CVOs and how pathogens can potentially enter the brain via these structures.Trial registrationNetherlands Trial Register number: NL6358, date of registration: 2017-03-24

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WED 168 Blood-brain barrier imaging with dynamic contrast-enhanced mri

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2018-abn.76 ◽

2018 ◽

Vol 89 (10) ◽

pp. A21.2-A21

Author(s):

Varatharaj Aravinthan ◽

Liljeroth Maria ◽

Darekar Angela ◽

BW Larsson Henrik ◽

Galea Ian ◽

...

Keyword(s):

White Matter ◽

Blood Brain Barrier ◽

Cerebral Blood Volume ◽

Brain Barrier ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Normal Appearing White Matter ◽

Blood Brain ◽

Contrast Enhanced ◽

Bbb Permeability

BackgroundDynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can detect subtle blood-brain barrier (BBB) permeability. We developed a protocol and conducted experiments to validate the technique.Methods12 subjects with relapsing-remitting multiple sclerosis (RRMS) and 13 controls were recruited. Whole-brain 3D DCE-MRI at 3 Tesla was used to calculate the influx constant Ki (Patlak method). Values were derived for manual regions of interest (ROI) as well as segmented tissue masks. In controls, cerebral blood volume (CBV) was measured in grey and white matter.ResultsIn RRMS, Ki in visibly-enhancing lesions was significantly higher than in normal-appearing white matter (NAWM) (p=0.002). Ki in NAWM was significantly higher in RRMS than controls, by both ROI (p=0.014) and segmentation (p=0.019) methods. In controls, Ki was significantly higher in grey than white matter (p=0.001). CBV (and therefore vascular surface area) was also significantly higher in grey matter (p=0.005), with a mean ratio of 1.9.ConclusionsOur method produces results in line with the expected behaviour of a BBB permeability marker, and the grey/white matter CBV ratio is in agreement with the histologically-established value.

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Accurate Determination of Blood–Brain Barrier Permeability Using Dynamic Contrast-Enhanced T1-Weighted MRI: A Simulation and in vivo Study on Healthy Subjects and Multiple Sclerosis Patients

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.126 ◽

2014 ◽

Vol 34 (10) ◽

pp. 1655-1665 ◽

Cited By ~ 57

Author(s):

Stig P Cramer ◽

Henrik BW Larsson

Keyword(s):

Blood Brain Barrier ◽

Temporal Resolution ◽

Brain Barrier ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Accuracy And Precision ◽

Contrast Enhanced ◽

Measurement Duration

Dynamic contrast-enhanced magnetic resonance imaging (DCE–MRI) is increasingly used to estimate permeability in situations with subtle blood–brain barrier (BBB) leakage. However, the method's ability to differentiate such low values from zero is unknown, and no consensus exists on optimal selection of total measurement duration, temporal resolution, and modeling approach under varying physiologic circumstances. To estimate accuracy and precision of the DCE–MRI method we generated simulated data using a two-compartment model and progressively down-sampled and truncated the data to mimic low temporal resolution and short total measurement duration. Model fit was performed with the Patlak, the extended Tofts, and the Tikhonov two-compartment (Tik-2CM) models. Overall, 17 healthy controls were scanned to obtain in vivo data. Long total measurement duration (15 minutes) and high temporal resolution (1.25 seconds) greatly improved accuracy and precision for all three models, enabling us to differentiate values of permeability as low as 0.1 ml/100 g/min from zero. The Patlak model yielded highest accuracy and precision for permeability values <0.3 ml/100 g/min, but for higher values the Tik-2CM performed best. Our results emphasize the importance of optimal parameter setup and model selection when characterizing low BBB permeability.

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7T dynamic contrast‐enhanced MRI for the detection of subtle blood–brain barrier leakage

Journal of Neuroimaging ◽

10.1111/jon.12894 ◽

2021 ◽

Author(s):

Lisanne P. W. Canjels ◽

Jacobus F. A. Jansen ◽

Marieke Kerkhof ◽

Robert‐Jan Alers ◽

Benedikt A. Poser ◽

...

Keyword(s):

Blood Brain Barrier ◽

Brain Barrier ◽

Dynamic Contrast Enhanced Mri ◽

Dynamic Contrast Enhanced ◽

Blood Brain ◽

Enhanced Mri ◽

Contrast Enhanced ◽

Contrast Enhanced Mri

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The Use of Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Evaluation of Blood-Brain Barrier Disruption in Traumatic Brain Injury: What Is the Evidence?

Brain Sciences ◽

10.3390/brainsci11060775 ◽

2021 ◽

Vol 11 (6) ◽

pp. 775

Author(s):

Sung-Suk Oh ◽

Eun-Hee Lee ◽

Jong-Hoon Kim ◽

Young-Beom Seo ◽

Yoo-Jin Choo ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Traumatic Brain Injury ◽

Brain Injury ◽

Magnetic Resonance ◽

Blood Brain Barrier ◽

Brain Barrier ◽

Resonance Imaging ◽

Dce Mri ◽

Dynamic Contrast Enhanced ◽

Contrast Enhanced

(1) Background: Blood brain barrier (BBB) disruption following traumatic brain injury (TBI) results in a secondary injury by facilitating the entry of neurotoxins to the brain parenchyma without filtration. In the current paper, we aimed to review previous dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to evaluate the occurrence of BBB disruption after TBI. (2) Methods: In electronic databases (PubMed, Scopus, Embase, and the Cochrane Library), we searched for the following keywords: dynamic contrast-enhanced OR DCE AND brain injury. We included studies in which BBB disruption was evaluated in patients with TBI using DCE-MRI. (3) Results: Four articles were included in this review. To assess BBB disruption, linear fit, Tofts, extended Tofts, or Patlak models were used. KTrans and ve were increased, and the values of vp were decreased in the cerebral cortex and predilection sites for diffusion axonal injury. These findings are indicative of BBB disruption following TBI. (4) Conclusions: Our analysis supports the possibility of utilizing DCE-MRI for the detection of BBB disruption following TBI.

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