Amide proton transfer-weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different institutes, and there are no agreed-on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi-center trials in larger patient cohorts and, ultimately, routine clinical use. K E Y W O R D APTw standardization, APT-weighted imaging, brain tumor, CEST imaging How to cite this article: Zhou J, Zaiss M, Knutsson L, et al. Review and consensus recommendations on clinical APT-weighted imaging approaches at 3T: Application to brain tumors.

No abstract

Size-Tunable, Ultrasmall NaGdF 4 Nanoparticles: Insights into Their T 1 MRI Contrast Enhancement. -Paramagnetic β-NaGdF4 nanoparticles are synthesized by addition of a MeOH solution containing NaOH and NH4F to a mixture of GdCl3, oleic acid, and octadecene. The size of the nanoparticles can precisely be controlled by varying reaction time and temperature. Particles of 2.5 nm sizes are obtained at 260°C for 10 min, 4.0 nm sized particles at 270°C for 40 min, 6.5 nm sized particles at 280°C for 90 min, and 8.0 nm particles at 285°C for 100 min. The prepared nanoparticles show magnetic resonance longitudinal relaxitivities per nanoparticle at 1.5 T which are 200-3000 times larger than that of the clinically used Gd-DTPA contrast agent, showing great potential as local contrast enhancement probes. β-NaGdF4 nanoparticles are good hosts for upconverting emission which is demonstrated by the preparation of luminescent ultrasmall β-NaGdF4:Yb 3+ /Tm 3+ nanoparticles as potential bimodal probes. -(JOHNSON, N. J. J.; OAKDEN, W.; STANISZ, G. J.; PROSSER, R. S.; VAN VEGGEL*, F. C. J. M.; Chem. Mater. 23 (2011) 16, 3714-3722, http://dx.

No abstract

Cellular apoptosis, a common pathway towards tumor regression, is induced by many radiotherapy and chemotherapy regimens. Imaging methods that can detect apoptosis may be able to assess treatment response earlier than typical tumor volume measurements. In this paper, a wide range of diffusion experiments and a simple model of diffusion in tissues were used to probe the microstructural effects of apoptosis. Experiments were conducted on acute myeloid leukemia cell pellets, where apoptosis was induced by treatment with the chemotherapeutic agent cisplatin. Seventy-two hours following cisplatin treatment, pulsed and oscillating gradient diffusion measurements were utilized to assess effects across a broad range of structural scales. The presence of apoptosis, which was histologically confirmed by TUNEL (terminal deoxynucleotidyl transferase UTP nick end labelling) staining, significantly changed diffusion properties. To describe these changes, the data were fit to the parallel plane model, which characterizes the effects of restricted diffusion in terms of three parameters: d, the restricted size, Dfree , the intrinsic, free diffusion coefficient of the solvent, and Drest , the long time or "restricted" diffusion coefficient. Apoptotic samples exhibited significant decreases in parameters d and Dfree and a significant increase in Drest . These changes appear consistent with the established morphological effects of apoptosis. In particular, the decrease in d may be a result of the combined effects of cell shrinkage, nuclear fragmentation and membrane blebbing, the decrease in Dfree may relate to cytosolic condensation, while the increase in Drest can be attributed to increased membrane permeability and extracellular volume fraction. By non-invasively detecting apoptosis, the methods reported in this study have the potential to improve upon current MRI methods for monitoring therapeutic response. Furthermore, these methods may offer sufficient specificity to differentiate between apoptosis and other modes of cell death, such as oncosis or necrosis.

No abstract

27The pathogenesis of spinal cord injury (SCI) remains poorly understood and treatment remains 28 limited. Emerging evidence indicates the severity of post-SCI inflammation and an ongoing 29 controversy in the roles of astrocytes with studies identifying astrocytes as associated both with 30 ongoing inflammation and damage as well as potentially having a protective role. We have 31 completed an extensive systematic study with MRI, histopathology, proteomics and ELISA 32 analyses designed to further define the severe protracted and damaging inflammation after SCI in 33 a rat model. We have identified 3 distinct phases of SCI: acute (first 2 days), inflammatory (starting 34 day 3) and resolution (>3 months) in 16 weeks follow up. Actively phagocytizing, CD68 + /CD163 -35 macrophages infiltrate myelin-rich necrotic areas converting them into cavities of injury (COI) 36 when deep in the spinal cord. Alternatively, superficial SCI areas are infiltrated by granulomatous 37 tissue, or arachnoiditis where glial cells are obliterated. In the COI, CD68+/CD163macrophage 38 numbers reach a maximum in the first 4 weeks and then decline. Myelin phagocytosis is present 39 at 16 weeks indicating ongoing inflammatory damage. The COI and arachnoiditis are defined by 40 a wall of progressively hypertrophied astrocytes. MR imaging indicates persistent spinal cord 41 edema that is linked to the severity of inflammation. Microhemorrhages in the spinal cord around 42 the lesion are eliminated, presumably by reactive astrocytes within the first week post-injury. 43Acutely increased levels of TNF-, IL-1, IFN- and other pro-inflammatory cytokines, 44 chemokines and proteases decrease and anti-inflammatory cytokines increase in later phases. In 45 this study we elucidated a number of fundamental mechanisms in pathogenesis of SCI and have 46 demonstrated a close association between progressive astrogliosis and reduction in the severity of 47 inflammation. 48 4 49 50 KEYWORDS 51 Neurotrauma inflammation, cavity of injury, arachnoiditis, M1 macrophage, astrogliosis. 5 52 53Spinal cord injury (SCI) is a leading cause of long term morbidity after motor vehicle 54 accidents or trauma in combat, with no clinically standardized or substantially effective treatment. 55Effective therapeutics have remained limited due to an incomplete understanding of the 56 pathogenesis of SCI and thus identified effective therapeutic targets while the underlying and 57 persistent inflammatory damage after SCI remains poorly characterized. The role of invasive 58 inflammatory cells and specifically astrogliosis in the ongoing damage after SCI is not fully 59 defined with studies supporting both a role in SCI damage [1,2] as well as a proposed potential 60 protective role for astrocytes [3]. We have completed an extensive analysis with MRI, 61 histochemistry, proteomics and ELISA in a rat model of SCI in order to further define the 62 pathological changes that occur after SCI. 63 SCI initiates hemorrhage and ischemia, free radical release, severe inflammation,...

The intestinal microbiome composition and dietary supplementation with psychobiotics can result in neurochemical alterations in the brain, which are possible due to the presence of the brain–gut–microbiome axis. In the present study, magnetic resonance spectroscopy (MRS) and behavioural testing were used to evaluate whether treatment with Lacticaseibacillus rhamnosus JB-1 (JB‑1) bacteria alters brain metabolites’ levels and behaviour during continuous exposure to chronic stress. Twenty Wistar rats were subjected to eight weeks of a chronic unpredictable mild stress protocol. Simultaneously, half of them were fed with JB-1 bacteria, and the second half was given a daily placebo. Animals were examined at three-time points: before starting the stress protocol and after five and eight weeks of stress onset. In the elevated plus maze behavioural test the placebo group displayed increased anxiety expressed by almost complete avoidance of exploration, while the JB-1 dietary supplementation mitigated anxiety which resulted in a longer exploration time. Hippocampal MRS measurements demonstrated a significant decrease in glutamine + glutathione concentration in the placebo group compared to the JB-1 bacteria-supplemented group after five weeks of stress. With the progression of stress the decrease of glutamate, glutathione, taurine, and macromolecular concentrations were observed in the placebo group as compared to baseline. The level of brain metabolites in the JB-1-supplemented rats were stable throughout the experiment, with only the taurine level decreasing between weeks five and eight of stress. These data indicated that the JB-1 bacteria diet might stabilize levels of stress-related neurometabolites in rat brain and could prevent the development of anxiety/depressive-like behaviour.