Contrast-enhanced in vivo magnetic resonance microscopy of the mouse brain enabled by noninvasive opening of the blood-brain barrier with ultrasound.

The use of contrast agents for neuroimaging is limited by the blood-brain barrier (BBB), which restricts entry into the brain. To administer imaging agents to the brain of rats, intracarotid infusions of hypertonic mannitol have been used to open the BBB. However, this technically challenging approach is invasive, opens only a limited region of the BBB, and is difficult to extend to mice. In this work, the BBB was opened in mice, using unfocused ultrasound combined with an injection of microbubbles. This technique has several notable features: it (a) can be performed transcranially in mice; (b) takes only 3 min and uses only commercially available components; (c) opens the BBB throughout the brain; (d) causes no observed histologic damage or changes in behavior (with peak-negative acoustic pressures of 0.36 MPa); and (e) allows recovery of the BBB within 4 h. Using this technique, Gadopentetate Dimeglumine (Gd-DTPA) was administered to the mouse brain parenchyma, thereby shortening T(1) and enabling the acquisition of high-resolution (52 × 52 × 100 micrometers(3)) images in 51 min in vivo. By enabling the administration of both existing anatomic contrast agents and the newer molecular/sensing contrast agents, this technique may be useful for the study of mouse models of neurologic function and pathology with MRI.

Imaging arrays with improved transmit power capability.

Bonded multilayer ceramics and composites incorporating low-loss piezoceramics have been applied to arrays for ultrasound imaging to improve acoustic transmit power levels and to reduce internal heating. Commercially available hard PZT from multiple vendors has been characterized for microstructure, ability to be processed, and electroacoustic properties. Multilayers using the best materials demonstrate the tradeoffs compared with the softer PZT5-H typically used for imaging arrays. Three-layer PZT4 composites exhibit an effective dielectric constant that is three times that of single layer PZT5H, a 50% higher mechanical Q, a 30% lower acoustic impedance, and only a 10% lower coupling coefficient. Application of low-loss multilayers to linear phased and large curved arrays results in equivalent or better element performance. A 3-layer PZT4 composite array achieved the same transmit intensity at 40% lower transmit voltage and with a 35% lower face temperature increase than the PZT-5 control. Although B-mode images show similar quality, acoustic radiation force impulse (ARFI) images show increased displacement for a given drive voltage. An increased failure rate for the multilayers following extended operation indicates that further development of the bond process will be necessary. In conclusion, bonded multilayer ceramics and composites allow additional design freedom to optimize arrays and improve the overall performance for increased acoustic output while maintaining image quality.

Dual-mode intracranial catheter integrating 3D ultrasound imaging and hyperthermia for neuro-oncology: feasibility study.

In this study, we investigated the feasibility of an intracranial catheter transducer with dual-mode capability of real-time 3D (RT3D) imaging and ultrasound hyperthermia, for application in the visualization and treatment of tumors in the brain. Feasibility is demonstrated in two ways: first by using a 50-element linear array transducer (17 mm x 3.1 mm aperture) operating at 4.4 MHz with our Volumetrics diagnostic scanner and custom, electrical impedance-matching circuits to achieve a temperature rise over 4 degrees C in excised pork muscle, and second, by designing and constructing a 12 Fr, integrated matrix and linear-array catheter transducer prototype for combined RT3D imaging and heating capability. This dual-mode catheter incorporated 153 matrix array elements and 11 linear array elements diced on a 0.2 mm pitch, with a total aperture size of 8.4 mm x 2.3 mm. This 3.64 MHz array achieved a 3.5 degrees C in vitro temperature rise at a 2 cm focal distance in tissue-mimicking material. The dual-mode catheter prototype was compared with a Siemens 10 Fr AcuNav catheter as a gold standard in experiments assessing image quality and therapeutic potential and both probes were used in an in vivo canine brain model to image anatomical structures and color Doppler blood flow and to attempt in vivo heating.