Robust MR assessment of cerebral blood volume and mean vessel size using SPION-enhanced ultrashort echo acquisition

Han, Sangwoo; Cho, J. H.; Jung, Haijo; Suh, Ji-Yeon; Kim, J. K.; Kim, Y. R.; Cho, G.; Cho, HyungJoon

doi:10.1016/j.neuroimage.2015.03.042

Cited by 17 publications

(20 citation statements)

References 47 publications

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“…Positive-contrast MRI experiments with iron oxide-labeled cells have been developed and are being investigated to address this problem but are not yet in common use. 8,26,27 There were also increased numbers of activated microglia existing in regions transplanted with the MIRB-labeled NSCs. This phenomenon was substantially more pronounced in the 50 μg case, compared to animals receiving 20 μg MIRB-labeled NSCs, and can be attributed to the observed reduced survival of the 50 μg grafts which led to the release of MIRB from dying cells.…”

mentioning

confidence: 98%

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Umashankar¹,

Corenblum²,

Ray³

et al. 2016

IJN

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An essential component of developing successful neural stem cell (NSC)-based therapies involves the establishment of methodologies to noninvasively monitor grafted NSCs within brain tissues in real time. In this context, ex vivo labeling with ultrasmall superparamagnetic iron oxide (USPIO) particles has been shown to enable efficient tracking of transplanted NSCs via magnetic resonance imaging (MRI). However, whether and how USPIO labeling affects the intrinsic biology of NSCs is not thoroughly understood, and remains an active area of investigation. Here, we perform a comprehensive examination of rat NSC survival and regenerative function upon labeling with the USPIO, Molday ION Rhodamine B (MIRB), which allows for dual magnetic resonance and optical imaging. After optimization of labeling efficiency, two specific doses of MIRB (20 and 50 μg/mL) were chosen and were followed for the rest of the study. We observed that both MIRB doses supported the robust detection of NSCs, over an extended period of time in vitro and in vivo after transplantation into the striata of host rats, using MRI and post hoc fluorescence imaging. Both in culture and after neural transplantation, the higher 50 μg/mL MIRB dose significantly reduced the survival, proliferation, and differentiation rate of the NSCs. Interestingly, although the lower 20 μg/mL MIRB labeling did not produce overtly negative effects, it increased the proliferation and glial differentiation of the NSCs. Additionally, application of this dose also changed the morphological characteristics of neurons and glia produced after NSC differentiation. Importantly, the transplantation of NSCs labeled with either of the two MIRB doses upregulated the immune response in recipient animals. In particular, in animals receiving the 50 μg/mL MIRB-labeled NSCs, this immune response consisted of an increased number of CD68 + -activated microglia, which appeared to have phagocytosed MIRB particles and cells contributing to an exaggerated MRI signal dropout in the animals. Overall, these results indicate that although USPIO particles, such as MIRB, may have advantageous labeling and magnetic resonance-sensitive features for NSC tracking, a further examination of their effects might be necessary before they can be used in clinical scenarios of cell-based transplantation.

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mentioning

confidence: 98%

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Umashankar¹,

Corenblum²,

Ray³

et al. 2016

IJN

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“…Hence, density could be used as a proxy to identify brain areas critical to the evolution of brain function and survival. Although similar techniques have been used to produce CBV measurements for larger gross regions of the brain (Han et al, 2015), here we show for the first time that combining QUTE-CE MRI with a detailed atlas provides new insights into brain structure and function, and demonstrates that changes between states can be measured. Other studies which have attempted to absolutely measure CBV on a regional basis have used less than 15 regions (Lear et al, 1990; Julien-Dolbec et al, 2002; Cremer and Seville, 1983; Everett et al, 1956; Adam et al, 2003; Chugh et al, 2009; Wu et al, 2004; Han et al, 2015; Schwarzbauer et al, 1997; Troprès et al, 2001; Watabe et al, 2013).…”

Section: Discussionmentioning

confidence: 79%

“…Although similar techniques have been used to produce CBV measurements for larger gross regions of the brain (Han et al, 2015), here we show for the first time that combining QUTE-CE MRI with a detailed atlas provides new insights into brain structure and function, and demonstrates that changes between states can be measured. Other studies which have attempted to absolutely measure CBV on a regional basis have used less than 15 regions (Lear et al, 1990; Julien-Dolbec et al, 2002; Cremer and Seville, 1983; Everett et al, 1956; Adam et al, 2003; Chugh et al, 2009; Wu et al, 2004; Han et al, 2015; Schwarzbauer et al, 1997; Troprès et al, 2001; Watabe et al, 2013). While ours is the first study to provide such regional detail, our findings closely fit the distributions of capillary density reported for Sprague-Dawley rats using [14C]2-deoxyglucose autoradiography (Schwartz and Sharp, 1978) and various morphometric techniques for measuring capillaries (Cavaglia et al, 2001; Zeller et al, 1997; Wagman Borowsky and Collins, 1989).…”

Section: Discussionmentioning

confidence: 79%

Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function

et al. 2017

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A method called Quantitative Ultra-Short Time-to-Echo Contrast Enhanced (QUTE-CE) Magnetic Resonance Imaging (MRI) which utilizes superparamagnetic iron oxide nanoparticles (SPI-ONs) as a contrast agent to yield positive contrast angiograms with high clarity and definition is applied to the whole live rat brain. QUTE-CE MRI intensity data are particularly well suited for measuring quantitative cerebral blood volume (qCBV). A global map of qCBV in the awake resting-state with unprecedented detail was created via application of a 3D MRI rat brain atlas with 173 segmented and annotated brain areas. From this map we identified two distributed, integrated neural circuits showing the highest capillary densities in the brain. One is the neural circuitry involved with the primary senses of smell, hearing and vision and the other is the neural circuitry of memory. Under isoflurane anesthesia, these same circuits showed significant decreases in qCBV suggesting a role in consciousness. Neural circuits in the brainstem associated with the reticular activating system and the maintenance of respiration, body temperature and cardiovascular function showed an increase in qCBV with anesthesia. During awake CO2 challenge, 84 regions showed significant increases relative to an awake baseline state. This CO2 response provides a measure of cerebralvascular reactivity and regional perfusion reserve with the highest response measured in the somatosensory cortex. These results demonstrate the utility of QUTE-CE MRI for qCBV analysis and offer a new perspective on brain function and vascular organization.

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“…Monte Carlo simulation was performed to verify the effects of acquisition voxel size to the measured T 2 and

{normalT}_{2}^{*}

relaxation times. The simulation was implemented using in‐house developed MATLAB scripts (MathWorks, Natick, MA) on an R2016b environment, based on the finite perturber method and previously described procedures . The magnetic field shift (ΔB) was calculated as the sum of the magnetic field shifts due to the finite perturbers (voxels in trabecular bone regions).…”

Section: Methodsmentioning

confidence: 99%

The robustness of T₂ value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI

Lee

Song

Park

et al. 2018

Magnetic Resonance in Med

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Robust MR assessment of cerebral blood volume and mean vessel size using SPION-enhanced ultrashort echo acquisition

Cited by 17 publications

References 47 publications

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function

The robustness of T₂ value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI

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Robust MR assessment of cerebral blood volume and mean vessel size using SPION-enhanced ultrashort echo acquisition

Cited by 17 publications

References 47 publications

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Effects of the iron oxide nanoparticle Molday ION Rhodamine B on the viability and regenerative function of neural stem cells: relevance to clinical translation

Quantitative vascular neuroimaging of the rat brain using superparamagnetic nanoparticles: New insights on vascular organization and brain function

The robustness of T2 value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI

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The robustness of T₂ value as a trabecular structural index at multiple spatial resolutions of 7 Tesla MRI