Abstract: Methods and systems for improving or enabling delivery of antibodies, immunoglobulin receptors, or immunotherapy agents across the Blood-Brain Barrier (BBB) are disclosed. Exosomes are derived from stem cells, immune cell progenitors, or immune cells, and are loaded with an antibody, immunoglobulin receptor, or antibody fragment. Focused energy, preferably low-intensity focused ultrasound, is applied to a region of the BBB of a patient, and loaded exosomes are administered to the patient. Exosomes target the region for delivery of the loaded antibody, receptor, or fragment, either by traversing the BBB at the region or releasing the loaded antibody to neural tissue at the region.

Abstract: Systems, methods, and devices are disclosed for administering a therapeutic agent to a patient and improving therapeutic effects of such agents on a patient. A stimulation is applied to a portion of a patient's spine, and the therapeutic agent is administered to the patient intrathecally and proximal to the portion of the patient's spine. In some embodiments, a second stimulation is applied to the patient at a second portion of the patient's spine and concurrently with administering the therapeutic agent. Concerted stimulation of the patient's spine administering a therapeutic agent synergistically improves treatment outcome.

Abstract: Apparatus, systems, and methods for comparative analysis of tissue and organ scans between patients or groups of patients without sensitivity to patient-specific or scanner specific characteristics, including prediction, diagnosis, prognosis, tracking, and treatment guidance are disclosed. Blood oxygen level dependent (BOLD) fMRI is performed on a patient, and the resulting structural and functional data is preprocessed to remove artifacts and correct motion defects. A BOLD value is selected from the Vein of Galen as the maximum anatomically plausible intensity and from the Middle Cerebral Artery as the minimum anatomically plausible intensity. The maximum and minimum intensities are used to normalize the BOLD data and generate a neurovascular coupling statistical map of the brain.

Abstract: Systems and methods are contemplated for monitoring and analyzing the glymphatic system and brain to predict, prognose, diagnose, treat, modify or improve treatment, and track progression of neurological diseases. A first and second MRI image are taken of an extracellular space in a region of interest in a patient's brain, with one image taken while the patient is awake and the other image taken while the patient is asleep. The first and second images are compared to detect changes in the extracellular space, and the comparison is used to predict, prognose, diagnose, treat, modify or improve treatment, and track progression of neurological diseases associated with the extracellular space.

Abstract: Methods, systems, and devices are disclosed for facilitating delivery of microvesicles or stem cells across the blood brain barrier (BBB). A pressure device is used to target a region of a patient's brain. The pressure device delivers a shockwave to the targeted region, facilitating delivery of a microvesicle or stem cell at the targeted region. The shockwave does not damage brain tissue and does not disrupt or tear the BBB. A microvesicle or stem cell, or both, is administered to the patient and crosses the BBB at the targeted region, without damaging, tearing, or disrupting the BBB.

Abstract: Methods, systems, and devices are disclosed for therapeutic stimulation of targeted regions of the brain, improved delivery of exosomes across the blood brain barrier, or combinations thereof. An ultrasound transducer is used to target a region of therapeutic interest in a patient's brain. The transducer sonicates the targeted region, forming openings in the blood brain barrier or increasing local perfusion at the targeted region. Near-infrared light sources can further be applied to the targeted region to increase delivery of exosomes, either in combination with sonic transducers. In some embodiments, near-infrared light sources are applied to the targeted region to regulate neurobiological function or encourage neurotherapeutic effects, either alone or in combination with the administration of exosomes or therapeutic agents to the patient.

Abstract: Systems, methods, and devices for administering, improving administration, or enabling the selective delivery of an agent to a target portion of a tissue are disclosed. An MRI device, at least high strength (e.g., at least 3 T), more preferably ultra high strength (e.g., at least 10 T) is directed at and applied to a target portion of a tissue, preferably brain tissue. A magnetic field is applied to the target portion of the tissue, selectively increasing local temperature and not impacting core temperature. The agent, preferably exosome carrying a therapeutic, is administered to the patient, and the agent is selectively delivered to the target portion of the tissue. Magnetic fields are optionally applied to the target portion before, during, or after administering the agent, or combinations thereof.

Abstract: Methods, devices, and systems are disclosed for affixing and orienting an ultrasound transducer to a patient. A mount has a base, with a top surface, a bottom surface, an outer surface, and a plurality of internal surfaces. Some of the internal surfaces define a number of through holes that pass through the top surface and the bottom surface at the periphery or outer edge of the base. A number of supports are also arranged on the outer surface of the housing to affix the mount to the patient, to affix the transducer to the mount, or both. At least one of the plurality of internal surfaces defines a channel between the top and bottom surfaces proximal to a center of the mount, which receives a transducer and directs the transducer head toward the patient.

Abstract: The improvement of administration of a therapeutic agent to a targeted region of a patient's brain is herein described. A magnetic material, preferably soluble iron, is administered to the patient. A magnetic field, for example via transcranial magnetic stimulation (TMS), is applied to the targeted region of the patient's brain. The magnetic field is used to agitate magnetic material localized to the targeted region of the brain, temporarily forming openings in the blood-brain barrier (BBB), increasing local perfusion, or both at the targeted region. A therapeutic agent is administered to the patient and is delivered to the targeted region of the patient's brain through openings in the BBB, local perfusion, or both.

Abstract: Systems, methods, and devices for administering, improving administration, or enabling the selective delivery of an agent to a target portion of a tissue are disclosed. An MRI device, at least high strength (e.g., at least 3 T), more preferably ultra high strength (e.g., at least 10 T) is directed at and applied to a target portion of a tissue, preferably brain tissue. A magnetic field is applied to the target portion of the tissue, selectively increasing local temperature and not impacting core temperature. The agent, preferably exosome carrying a therapeutic, is administered to the patient, and the agent is selectively delivered to the target portion of the tissue. Magnetic fields are optionally applied to the target portion before, during, or after administering the agent, or combinations thereof.

Abstract: Systems, methods, and devices are disclosed for administering a therapeutic agent to a patient and improving therapeutic effects of such agents on a patient. A stimulation is applied to a portion of a patient's spine, and the therapeutic agent is administered to the patient intrathecally and proximal to the portion of the patient's spine. In some embodiments, a second stimulation is applied to the patient at a second portion of the patient's spine and concurrently with administering the therapeutic agent. Concerted stimulation of the patient's spine administering a therapeutic agent synergistically improves treatment outcome.

Abstract: Methods, devices, and systems are disclosed for affixing and orienting an ultrasound transducer to a patient. A mount has a base, with a top surface, a bottom surface, an outer surface, and a plurality of internal surfaces. Some of the internal surfaces define a number of through holes that pass through the top surface and the bottom surface at the periphery or outer edge of the base. A number of supports are also arranged on the outer surface of the housing to affix the mount to the patient, to affix the transducer to the mount, or both. At least one of the plurality of internal surfaces defines a channel between the top and bottom surfaces proximal to a center of the mount, which receives a transducer and directs the transducer head toward the patient.

Abstract: Systems and methods are contemplated for monitoring and analyzing the glymphatic system and brain to predict, prognose, diagnose, treat, modify or improve treatment, and track progression of neurological diseases. A first and second MRI image are taken of an extracellular space in a region of interest in a patient's brain, with one image taken while the patient is awake and the other image taken while the patient is asleep. The first and second images are compared to detect changes in the extracellular space, and the comparison is used to predict, prognose, diagnose, treat, modify or improve treatment, and track progression of neurological diseases associated with the extracellular space.

Abstract: Methods, devices, and systems are disclosed for treating patients with ultrasound targeted at regions of the brain. An ultrasound transducer is positioned on a patient's head to target a region of the patient's brain for ultrasound therapy. An ultrasound wave is emitted at the target region of the patient's brain. At least partially concurrently, a fMRI imaging device generates real time images of activity in the patient's brain, for example by ASL protocol, BOLD protocol, or a combination thereof. Activity in the patient's brain caused by the ultrasound wave is detected, typically a distance ? from the target region. The transducer is repositioned or reoriented to correct for ? and better target the region, and another series of ultrasound waves are directed at the target region with improved accuracy.

Abstract: Systems, methods, and devices for mapping brain activity to identify therapeutic targets in a patient are disclosed. A set of stimuli is applied to the patient, which includes stimulus that are at least one of provocative, soothing, or neutral with respect to a condition of a patient, for example addiction, phobia, disorder, etc. The patient focuses on one of the stimuli, in some embodiments suppressing the patient's mental or emotional response to the stimuli. As the patient responds to the stimuli, the patient's brain activity is monitored, for example by fMRI. After presenting a series of sets of stimuli to the patient and monitoring the patient's brain activity responsive to the stimuli, the brain activity is mapped to the condition based on the type of stimuli corresponding to the brain activity.

Abstract: Methods, systems, and devices are disclosed for improving administration of a therapeutic agent to a targeted region of a patient's brain. A magnetic material, preferably soluble iron, is administered to the patient. A magnetic field, for example via transcranial magnetic stimulation (TMS), is applied to the targeted region of the patient's brain. The magnetic field is used to agitate magnetic material localized to the targeted region of the brain, temporarily forming openings in the blood-brain barrier (BBB), increasing local perfusion, or both at the targeted region. A therapeutic agent is administered to the patient and is delivered to the targeted region of the patient's brain through openings in the BBB, local perfusion, or both.

Abstract: Methods, systems, and devices are disclosed for therapeutic stimulation of targeted regions of the brain, improved delivery of exosomes across the blood brain barrier, or combinations thereof. An ultrasound transducer is used to target a region of therapeutic interest in a patient's brain. The transducer sonicates the targeted region, forming openings in the blood brain barrier or increasing local perfusion at the targeted region. Near-infrared light sources can further be applied to the targeted region to increase delivery of exosomes, either in combination with sonic transducers. In some embodiments, near-infrared light sources are applied to the targeted region to regulate neurobiological function or encourage neurotherapeutic effects, either alone or in combination with the administration of exosomes or therapeutic agents to the patient.

Abstract: Apparatus, systems, and methods for comparative analysis of tissue and organ scans between patients or groups of patients without sensitivity to patient-specific or scanner specific characteristics, including prediction, diagnosis, prognosis, tracking, and treatment guidance are disclosed. Blood oxygen level dependent (BOLD) fMRI is performed on a patient, and the resulting structural and functional data is preprocessed to remove artifacts and correct motion defects. A BOLD value is selected from the Vein of Galen as the maximum anatomically plausible intensity and from the Middle Cerebral Artery as the minimum anatomically plausible intensity. The maximum and minimum intensities are used to normalize the BOLD data and generate a neurovascular coupling statistical map of the brain.

Abstract: Abnormal functioning of the dorsal lateral prefrontal cortex (DLPF) has been implicated in depression. Repetitive Transcranial Magnetic Stimulation (rTMS) of the DLPF has been successful in treating depression, however, successful translation to routine clinical practice has shown modest results using standard protocols. The present invention provides paradigms, systems, and methods for the targeted, location specific, and pulse-modulated treatment of conditions such as depression, anxiety, OCD, chronic pain syndromes, drug and alcohol addiction, and other conditions through the use of advanced functional MRI (fMRI) or PET/CT, stereotactic neuronavigation, and the performance of cognitive tasks with the maximally efficient delivery of rTMS pulses, which can be varied and precisely targeted, to obtain concurrent activation of targeted brain networks.