Biology subjects

Odeen, H.

Publications and source records attributed to Odeen, H..

4 recordsLinked to original sources

bioRxiv2025

The insidious degeneration of white matter and cognitive decline in Fabry disease

Fabry disease is a rare X-linked deficiency of lysosomal alpha-galactosidase that causes glycolipid accumulation in tissues, including the brain. The most common neurologic sequelae of Fabry are cognitive decline and white matter lesions (WMLs) on brain magnetic resonance imaging (MRI). In the at-large population, however, WMLs are non-specific, highly prevalent, and most are clinically silent. Thus, we compared Fabry to typical brain aging to identify factors unique to Fabry-related cognitive decline. Twenty adult Fabry patients (75% female; median age 36.4 yrs, range: 19.8-63.2 yrs; 95% on enzyme replacement therapy) without a history of stroke or other neurologic diseases and 20 age/sex-matched healthy controls were enrolled in a case-control study. All participants underwent a neurocognitive assessment and a 3.0 T MRI study of the brain that used structural MRI (e.g., fluid-attenuated inversion recovery, FLAIR), semi-quantitative MRI (e.g., normalized FLAIR signal intensity), and quantitative MRI (diffusion tensor imaging, bound-pool fraction imaging). During a blinded review of structural MRIs, a neuroradiologists categorization of case-control status did not correspond to disease status (Fishers test, P>0.99) but rather to age (P=0.004), indicating qualitative changes associated with Fabry were similar to normal age-related brain alterations. Using quantitative MRI, however, we detected evidence of microstructural damage in the white matter of younger Fabry adults (<40 yrs). With age, WML severity increased and the corpus callosum atrophied in Fabry, phenomena absent in controls and consistent with progressive tissue damage. Neurocognitive assessments identified trends for lower verbal intelligence quotient and executive function in the younger Fabry participants, which became statistically significant in the older Fabry cohort. Our data indicate that the early onset of microstructural damage in Fabry drives the insidious degeneration of white matter, leading to reduced cognition. Aging Fabry patients may benefit from serial cognitive assessments to identify unmet therapeutic needs.

genetics↗

bioRxiv2023

Development of an MR-guided focused ultrasound (MRgFUS) lesioning approach for small and deep structures in the rat brain

ObjectiveHigh-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a noninvasive therapy to lesion brain tissue, used clinically in patients and preclinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of [~]0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. MethodsThe study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n=7 lesions) was compared to a craniectomy approach (n=22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. ResultsComparing a motorized adjustment system ([~]1 mm precision, n=17 lesions) to the motorized system with an added micromanipulator ([~]0.1 mm precision, n=14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models.

bioengineering↗

bioRxiv2023

Remotely controlled drug release in deep brain regionsof non-human primates

Many areas of science and medicine would benefit from selective release of drugs in specific regions of interest. Nanoparticle drug carriers activated by focused ultrasound--remotely applied, depth-penetrating energy--may provide such selective interventions. Here, we developed stable, ultrasound-responsive nanoparticles that can be used to release drugs effectively and safely in non-human primates. The nanoparticles were used to release propofol in deep brain visual regions. The release reversibly modulated the subjects visual choice behavior and was specific to the targeted region and to the released drug. Gadolinium-enhanced MRI imaging suggested an intact blood-brain barrier. Blood draws showed normal clinical chemistry and hematology. In summary, this study provides a safe and effective approach to release drugs on demand in selected deep brain regions at levels sufficient to modulate behavior. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=61 SRC="FIGDIR/small/561539v3_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@1c4c3acorg.highwire.dtl.DTLVardef@10a5e6borg.highwire.dtl.DTLVardef@1bce636org.highwire.dtl.DTLVardef@adf9a8_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Noninvasive, Systematic, and Sustained Modulation of Deep Brain Circuits in Awake Subjects

Transcranial focused ultrasound has the potential to noninvasively and systematically modulate deep brain circuits and impart sustained, neuroplastic effects in awake subjects. The intersection of these properties is critical for effective treatments of brain disorders, yet remains to be shown. Harnessing the full potential of transcranial ultrasound, we delivered 30-second stimuli into deep brain targets (left/right lateral geniculate nucleus) of non-human primates while they performed a visual discrimination task. This brief stimulation induced sustained and target-specific behavioral preference that persisted up to 15 minutes following the ultrasound offset. The polarity of the behavioral and neural effects suggested that ultrasound excited the stimulated circuits. The ultrasound was delivered into the deep brain daily for a period of more than 6 months, which enabled us to evaluate the safety of longterm stimulation. There were no detrimental effects on the animals discrimination accuracy over the course of this stimulation regimen. This study demonstrates ultrasounds capacity to condition deep brain circuits in a safe and treatment-relevant manner in awake subjects, and provides a basis for effective and safe translations into humans. HighlightsO_LITranscranial ultrasound induces effective and sustained modulation of deep brain circuits. C_LIO_LIThe deep brain modulation biases choice behavior of non-human primates. C_LIO_LIThe deep brain modulation produces sustained elevation of high gamma activity. C_LIO_LIThe stimulation, applied daily for several months, is safe. C_LI

neuroscience↗