Ultrasonically Produced Changes in the Blood-Brain Barrier

Bakay, Louis; Hueter, T. F.; Ballantine, H. Thomas; Sosa, D. M.

doi:10.1001/archneurpsyc.1956.02330290001001

Cited by 133 publications

(72 citation statements)

References 7 publications

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“…Neuronal damage with BBB opening induced by ultrasound at or near ablation intensities was initially reported in some studies (Bakay et al 1956 ;Ballantine et al 1960 ;Patrick et al 1990 ) but not in others (Vykhodtseva et al 1995 ). After reducing the acoustic intensity and duty cycle, BBB opening was still observed, but macroscopic damage was avoided (Mesiwala et al 2002 ).…”

Section: Bbb Opening Using Fus and Microbubblesmentioning

confidence: 97%

Emerging Engineering Technologies for Opening the BBB

Konofagou

2013

Drug Delivery to the Brain

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Current treatments of neurological and neurodegenerative diseases are limited due to the lack of a truly noninvasive, transient, and regionally selective brain drug delivery method. The brain is particularly diffi cult to deliver drugs to because of the blood-brain barrier (BBB). The impermeability of the BBB is due to the tight junctions between adjacent endothelial cells and highly regulatory transport systems of the endothelial cell membranes. The main function of the BBB is ion and volume regulation to ensure the conditions necessary for proper synaptic and axonal signaling. However, the same permeability properties that keep the brain healthy also present tremendous obstacles to its pharmacological treatment. Until a solution to the trans-BBB delivery problem is found, treatments of neurological diseases will remain impeded. Over the past decade, methods that combine focused ultrasound (FUS) and microbubbles have been shown to offer the unique capability to noninvasively, locally, and transiently open the BBB. Four of the main challenges to the application of FUS are (1) to assess its safety profi le, (2) to unveil the mechanism by which the BBB opens and closes, (3) to control and predict the opened BBB properties and duration of the opening, and (4) to assess its promise for brain drug delivery. In this chapter, we discuss all of these challenges, along with fi ndings in both small (mice) and large (nonhuman primates) animals, and emphasize the clinical potential for this technique.

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Section: Bbb Opening Using Fus and Microbubblesmentioning

confidence: 97%

Emerging Engineering Technologies for Opening the BBB

Konofagou

2013

Drug Delivery to the Brain

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“…Although they concluded that, given their configuration, it was not possible to produce permanent changes in the brain without undesired damage, they speculated that modifications such as removal of the skull bone and use of multiple focused beams could make such treatment possible. Ensuing investigations, performed after craniotomy, indicated the ability to produce discrete deep lesions in the brain [3][4][5][6][7][8] as well as an ability to open the blood-brain barrier [9] in a targeted region.…”

Section: Early Researchmentioning

confidence: 99%

“…Significant attention has recently focused on the ability of ultrasound to temporarily open the bloodbrain barrier (Figure 6), providing a means for spatially targeted and time-windowed passage of therapeutic agents into the brain. It has long been recognized that ultrasound can disrupt the bloodbrain barrier [9] but the prospect of creating a controlled reversible process [80], introduces significant promise for delivering agents that currently cannot be delivered into the brain. Furthermore, the prospect of targeting may protect certain areas in the brain while providing benefit to the target.…”

Section: Future Applicationsmentioning

confidence: 99%

Clinical applications of focused ultrasound—The brain

Hynynen

Clement

2007

International Journal of Hyperthermia

121

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“…found that 'Histological examination of lesions stained by trypan blue showed this method to be a reliable index of the area of tissue damage.' In this same connexion Bakay et al (1956) state that 'The lesion area does not seem to change in size during the first few days after irradiation. There is evidence of an additional zone of edema showing faint blue discolouration during the first two hours.…”

mentioning

confidence: 92%

“…After irradiation the wound was closed and 5-0 ml. of 2 % solution of trypan blue in 0-45 % saline was administered by slow intravenous injection to demarcate the areas of destruction (Bakay, Hueter, Ballantine & Sosa, 1956). …”

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confidence: 99%

A simple method for production of trackless focal lesions with focused ultrasound: statistical evaluation of the effects of irradiation on the central nervous system of the cat

Basauri¹,

Lele²

1962

The Journal of Physiology

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In a previous paper (Lele, 1962b) it has been shown that by irradiation with a single beam of focused ultrasound it is possible to produce trackless focal alterations of predetermined size at any desired location within a relatively homogeneous and stable medium. This paper will present the results obtained by application of ultrasound, under comparable experimental conditions, to the brain of the cat in a statistical manner and will discuss its potentialities and limitations as an experimental tool. More specifically, it will deal with (1) the relation between ultrasonic dosage and lesion size in different target areas and under controlled experimental conditions, with special reference to the range of deviation that was encountered; and (2) the statistical probability of accurately hitting a pre-determined discrete target in a blind experiment by the stereotaxic method. The neurophysiological effects of ultrasonic irradiation with subthreshold dosages in reference to its potential use for locating targets without inflicting any damage will be dealt with in a subsequent paper. METHODSA single beam of focused ultrasound at the frequency of 2-7 Mc/s subtending a solid angle of 420 in degassed water at 370C as described previously (Lele, 1962a) was used in this investigation. Focal characteristics of the irradiation system were checked at monthly intervals, by determination of energy distribution in the focal plane perpendicular to the main axis of irradiation (see 'lateral scan', Lele, 1962a). Intensity was set to the desired level by means of the radiation pressure gauge ('Sonar Test') before every irradiation and was checked again immediately after the experiment. Recordings of the oscillator cathode current were made after setting the intensity level and during irradiation. The temperature of the irradiation head was maintained at 370 C by immersion into a thermostatically controlled water-bath.

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Ultrasonically Produced Changes in the Blood-Brain Barrier

Cited by 133 publications

References 7 publications

Emerging Engineering Technologies for Opening the BBB

Emerging Engineering Technologies for Opening the BBB

Clinical applications of focused ultrasound—The brain

A simple method for production of trackless focal lesions with focused ultrasound: statistical evaluation of the effects of irradiation on the central nervous system of the cat

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