SUMMARYObjective: Hippocampal sclerosis (HS) is the major structural brain lesion in patients with temporal lobe epilepsy (TLE). However, its internal anatomic structure remains difficult to recognize at 1.5 or 3 Tesla (T) magnetic resonance imaging (MRI), which allows neither identification of specific pathology patterns nor their proposed value to predict postsurgical outcome, cognitive impairment, or underlying etiologies. We aimed to identify specific HS subtypes in resected surgical TLE samples on 7T MRI by juxtaposition with corresponding histologic sections. Methods: Fifteen nonsclerotic and 18 sclerotic hippocampi were studied ex vivo using an experimental 7T MRI scanner. T 2 -weighted images (T2wi) and diffusion tensor imaging (DTI) data were acquired and validated using a systematic histologic analysis of same specimens along the anterior-posterior axis of the hippocampus. Results: In nonsclerotic hippocampi, differences in MR intensity could be assigned to seven clearly recognizable layers and anatomic boundaries as confirmed by histology. All hippocampal subfields could be visualized also in the hippocampal head with threedimensional imaging and angulated coronal planes. Only four discernible layers were identified in specimens with histopathologically confirmed HS. All sclerotic hippocampi showed a significant atrophy and increased signal intensity along the pyramidal cell layer. Changes in DTI parameters such as an increased mean diffusivity, allowed to distinguish International League Against Epilepsy (ILAE) HS type 1 from type 2. Whereas the increase in T2wi signal intensities could not be attributed to a distinct specific histopathologic substrate, that is, decreased neuronal or increased glial cell densities, intrahippocampal projections and fiber tracts were distorted in HS specimens suggesting a complex disorganization of the cellular composition, fiber networks, as well as its extracellular matrix. Significance: Our data further advocate high-resolution MRI as a helpful and promising diagnostic tool for the investigation of hippocampal pathology along the anterior-posterior extent in TLE, as well as in other neurologic and neurodegenerative disorders.

Purpose Creatine (Cr) is a major metabolite in the bioenergetic system. Measurement of Cr using conventional MR spectroscopy (MRS) suffers from low spatial resolution and relatively long acquisition times. Creatine chemical exchange saturation transfer (CrCEST) magnetic resonance imaging (MRI) is an emerging molecular imaging method for tissue Cr measurements. Our previous study showed that the CrCEST contrast, obtained through multicomponent Z-spectral fitting, was lower in tumors compared to normal brain, which further reduced with tumor progression. The current study was aimed to investigate if CrCEST MRI can also be useful for differentiating gliomas with different degrees of aggressiveness. Procedures Intracranial 9L gliosarcoma and F98 glioma bearing rats with matched tumor size were scanned with a 9.4 T MRI scanner at two time points. CEST Z-spectra were collected using a customized sequence with a frequency-selective rectangular saturation pulse (B1 = 50 Hz, duration = 3 s) followed by a single-shot readout. Z spectral data were fitted pixel-wise with five Lorentzian functions, and maps of CrCEST peak amplitude, linewidth, and integral were produced. For comparison, single-voxel proton MR spectroscopy (1H-MRS) was performed to quantify and compare the total Cr concentration in the tumor. Results CrCEST contrasts decreased with tumor progression from weeks 3 to 4 in both 9L and F98 phenotypes. More importantly, F98 tumors had significantly lower CrCEST integral compared to 9L tumors. On the other hand, integrals of other Z-spectral components were unable to differentiate both tumor progression and phenotype with limited sample size. Conclusions Given that F98 is a more aggressive tumor than 9L, this study suggests that CrCEST MRI may help differentiate gliomas with different aggressiveness.

IntroductionBiglycan is an important proteoglycan of the extracellular matrix of intervertebral disc (IVD), and its decrease with aging has been correlated with IVD degeneration. Biglycan deficient (Bgn−/0) mice lack this protein and undergo spontaneous IVD degeneration with aging, thus representing a valuable in vivo model for preliminary studies on therapies for human progressive IVD degeneration. The purpose of the present study was to assess the possible beneficial effects of adipose-derived stromal cells (ADSCs) implants in the Bgn−/0 mouse model.MethodsTo evaluate ADSC implant efficacy, Bgn−/0 mice were intradiscally (L1-L2) injected with 8x104 ADSCs at 16 months old, when mice exhibit severe and complete IVD degeneration, evident on both 7Tesla Magnetic Resonance Imaging (7TMRI) and histology. Placebo and ADSCs treated Bgn−/0 mice were assessed by 7TMRI analysis up to 12 weeks post-transplantation. Mice were then sacrificed and implanted discs were analyzed by histology and immunohistochemistry for the presence of human cells and for the expression of biglycan and aggrecan in the IVD area.ResultsAfter in vivo treatment, 7TMRI revealed evident increase in signal intensity within the discs of mice that received ADSCs, while placebo treatment did not show any variation. Ultrastructural analyses demonstrated that human ADSC survival occurred in the injected discs up to 12 weeks after implant. These cells acquired a positive expression for biglycan, and this proteoglycan was specifically localized in human cells. Moreover, ADSC treatment resulted in a significant increase of aggrecan tissue levels.ConclusionOverall, this work demonstrates that ADSC implant into degenerated disc of Bgn−/0 mice ameliorates disc damage, promotes new expression of biglycan and increased levels of aggrecan. This suggests a potential benefit of ADSC implant in the treatment of chronic degenerative disc disease and prompts further studies in this field.

Purpose: To characterize the relaxation properties of reactive oxygen species (ROS) for the development of endogenous ROS contrast magnetic resonance imaging (MRI). Materials and Methods: ROS-producing phantoms and animal models were imaged at 9.4T MRI to obtain T 1 and T 2 maps. Egg white samples treated with varied concentrations of hydrogen peroxide (H 2 O 2 ) were used to evaluate the effect of produced ROS in T 1 and T 2 for up to 4 hours. pH and temperature changes due to H 2 O 2 treatment in egg white were also monitored. The influences from H 2 O 2 itself and oxygen were evaluated in bovine serum albumin (BSA) solution producing no ROS. In addition, dynamic temporal changes of T 1 in H 2 O 2 -treated egg white samples were used to estimate ROS concentration over time and hence the detection sensitivity of relaxation-based endogenous ROS MRI. The relaxivity of ROS was compared with that of Gd-DTPA as a reference. Finally, the feasibility of in vivo ROS MRI with T 1 mapping acquired using an inversion recovery sequence was demonstrated with a well-established rotenone-treated mouse model (n 5 6). Results: pH and temperature changes in treated egg white samples were insignificant (<0.1 unit and <18C, respectively). T 1 relaxation time in the H 2 O 2 -treated egg white was reduced significantly (P < 0.05), while there was only small reduction in T 2 (<10%). In the H 2 O 2 -treated BSA solution that produce no ROS, there was a small change in T 1 due to H 2 O 2 itself (61%), although a significant T 2 -shortening effect was observed (>10%, P < 0.05). Also, there was a small reduction in T 1 (13 6 1%) and T 2 (1 6 2%) from molecular oxygen. The detection sensitivity of ROS MRI was estimated around 10 pM. The T 1 relaxivity of ROS was found to be much higher than that of Gd-DTPA (3.4 3 10 7 vs. 0.9 s 21 ÁmM 21 ). Finally, significantly reduced T 1 was observed in rotenone-treated mouse brain (5.1 6 2.5%, P < 0.05). Conclusion: We demonstrated in the study that endogenous ROS MRI based on the paramagnetic effect has sensitivity for in vitro and in vivo applications. Level of Evidence: 2 Technical Efficacy Stage: 2 J. MAGN. RESON. IMAGING 2018;47:222-229. R eactive oxygen species (ROS), including singlet oxygen, and hydroxyl radical (ÁOH), have long been subjects of study due to their central role in cell signaling, the aging process, and in the pathogenesis of a variety of diseases such as cardiovascular diseases, diabetes, cancer, Alzheimer's, and Parkinson's diseases. 1-5 ROS can be divided into radical species (eg, ÁOH) and nonradical species (eg, H 2 O 2 ). They are mainly produced by several different enzyme systems (eg, cytosolic enzyme) and by the mitochondrial complex I and III. 6 They can react readily with any surrounding tissue component (eg, lipids, proteins, and DNA) 2 and can initiate complicated chain processes with high biological impact (eg, Haber-Weiss or Fenton reactions). 7 The high reactivity and short lifetime of radical ROS make them very challenging to detect. For example, the lifetime...

Gold nanoparticles coated with fluorinated ligands (F-MPCs) present features suitable for (19)F MRI as observed from phantom experiments. Cellular uptake, by HeLa cells, and toxicity of fluorescent dye-decorated F-MPCs are presented together with their ability to bind hydrophobic molecules allowing for a potential combination of targeting, delivery and imaging features.

Background: To implement omega plot method for in vivo mapping of proton exchange rates in human brain by taking into account the water direct saturation (DS) effect and multiple saturation transfer exchanging species in vivo.Methods: Four Z-spectra were collected with chemical exchange saturation transfer (CEST) saturation power =1, 2, 3 & 4 μT. Water DS was estimated by fitting the Z-spectrum to a linear combination of multiple Lorentzian components and its contribution to the signal was subsequently removed. Exchange rate maps were derived by the omega plot, consisting of fitting the inverse of the signal intensity, M z /(M 0 −M z ), as a function of 1/(γB 1 ) 2 . Results:The exchange rate values quantified with the DS removed omega plot were significantly higher in the GM region than in the WM region (616±29 vs. 575±20 s −1 , P<0.001). Phantom studies confirmed that the exchange rates from DS-removed plots varied linearly with pH (R 2 =0.998) for the pH range of 6.2 to 7.4, whereas exchange rates from conventional omega plots failed to show such linearity in the entire physiological pH range. Conclusions:The calculated exchange rate with DS-corrected omega plot is a weighted average for all saturation transfer exchanging proton species which contribute to Z-spectral signal. The healthy brain exchange rate map provided by DS-removed omega plots may serve as a baseline for detecting any pathological changes.

1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1527-1533.

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