Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study

Abstract Magnetic resonance imaging (MRI) is a promising diagnostic method for evaluation of bone marrow myelofibrosis for offering non-invasive, wider-area coverage over conventional histology. Although the most striking feature in histology of myelofibrotic bone marrow is the proliferation of reticulin fibers, the spectrum of findings involves abnormalities in cell number and composition, vessel proliferation, as well as possible pre-fibrotic abnormalities in matrix such as inflammation/edema. Correlation of MRI observations with such histological findings to accurately define the pathogenic phases of myelofibrosis has been challenging. Here, we present the first MRI analysis of myelofibrosis in a mouse model (Gata-1low mice) in an attempt to correlate MRI signal observations with histological findings. T2-weighted MRI images of femur bone marrow of Gata-1low animals at different ages (12 to 46 weeks) showed high MR signal intensity, absent in age-matched wild-type controls, that is detected as early as 12 weeks of age, before onset of histologically-defined fibrosis in this mouse model. MRI acquisitions employing fat suppression, a technique that suppresses signals from lipids, together with the absence of chemical shift artifacts in the images, excluded the possibility of lipids as the source of the prominent MR signal. To determine the source of this prominent non-lipid signal in Gata-1low bone marrow, cellular composition, vascularization and vascular permeability were tested. Our findings demonstrate a multi-source nature of MRI signals in bone marrow, which evolves from young (12 weeks) to old (40 weeks) Gata-1low bone marrow consistent with the pathologic progression of myelofibrosis. Data support the importance of an integrative approach to further the development of this non-invasive modality for following the dynamics and progression of this multifactorial pathology in humans. Disclosures No relevant conflicts of interest to declare.

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A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI)

Clinical Immunology ◽

10.1016/j.clim.2016.07.013 ◽

2016 ◽

Vol 172 ◽

pp. 52-60 ◽

Cited By ~ 4

Author(s):

Francesca Valdora ◽

Giovanna Cutrona ◽

Serena Matis ◽

Fortunato Morabito ◽

Carlotta Massucco ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Iron Oxide ◽

Magnetic Resonance ◽

Chronic Lymphocytic Leukemia ◽

Mouse Model ◽

Superparamagnetic Iron Oxide ◽

Lymphocytic Leukemia ◽

Resonance Imaging ◽

Invasive Approach ◽

Non Invasive

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A non-invasive digital biomarker for the detection of rest disturbances in the SOD1G93A mouse model of ALS

10.1101/2019.12.27.889246 ◽

2019 ◽

Cited By ~ 1

Author(s):

E. Golini ◽

M. Rigamonti ◽

F. Iannello ◽

C. De Rosa ◽

F. Scavizzi ◽

...

Keyword(s):

Body Weight ◽

Mouse Model ◽

Motor Neurons ◽

Sleep Disturbances ◽

Activity Patterns ◽

Non Invasive ◽

Younger Age ◽

Animal Activity ◽

Sod1g93a Mouse

AbstractAmyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that affects both central and peripheral nervous system, leading to the degeneration of motor neurons, which eventually results in muscle atrophy, paralysis and death. Sleep disturbances are common in patients with ALS, leading to even further deteriorated quality of life. Investigating methods to potentially assess sleep and rest disturbances in animal models of ALS is thus of crucial interest.We used an automated home cage monitoring system (DVC®) to capture activity patterns that can potentially be associated with sleep and rest disturbances and thus to the progression of ALS in the SOD1G93A mouse model. DVC® enables non-intrusive 24/7 long term animal activity monitoring, which we assessed together with body weight decline and neuromuscular function deterioration measured by grid hanging and grip strength tests in male and female mice from 7 until 24 weeks of age.We show that as the ALS progresses over time in SOD1G93A mice, activity patterns during day time start becoming irregular, with frequent activity bouts that are neither observed in control mice nor in SOD1G93A at a younger age. The increasing irregularities of activity patterns during day time are quantitatively captured by designing a novel digital biomarker, referred to as Rest Disturbance Index (RDI). We show that RDI is a robust measure capable of detecting rest/sleep-related disturbances during the disease progression earlier than conventional methods, such as the grid hanging test. Moreover RDI highly correlates with grid hanging and body weight decline, especially in males.The non-intrusive long-term continuous monitoring of animal activity enabled by DVC® has been instrumental in discovering activity patterns potentially correlated with sleep and rest disturbances in the SOD1G93A mouse model of the ALS disease.

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