A new ultrasound instrument for in vivo microimaging of mice.

We report here on the design and evaluation of the first high-frequency ultrasound (US) imaging system specifically designed for microimaging of the mouse. High-frequency US or US biomicroscopy (UBM) has the advantage of low cost, rapid imaging speed, portability and high resolution. In combination with the ability to provide functional information on blood flow, UBM provides a powerful method for the investigation of development and disease models. The new UBM imaging system is demonstrated for mouse development from day 5.5 of embryogenesis through to the adult mouse. At a frequency of 40 MHz, the resolution voxel of the new mouse scanner measures 57 microm x 57 microm x 40 microm. Duplex Doppler provides blood velocity sensitivity to the mm per s range, consistent with flow in the microcirculation, and can readily detect blood flow in the embryonic mouse heart, aorta, liver and placenta. Noninvasive UBM assessment of development shows striking similarity to invasive atlases of mouse anatomy. The most detailed noninvasive in vivo images of mouse embryonic development achieved using any imaging method are presented.

A high-frequency pulsed-wave Doppler ultrasound system for the detection and imaging of blood flow in the microcirculation.

Previous work with a 40-MHz continuous-wave Doppler ultrasound system has demonstrated the potential of high-frequency Doppler ultrasound (HFD), operating in the frequency range 20-200 MHz, to detect blood flow in the microcirculation. This paper describes a directional, pulsed-wave high-frequency Doppler ultrasound (PW HFD) system that was designed and constructed further to investigate this potential. The PW HFD system electronics have a dynamic range of > 80 dB, a noise floor of 250 nV, a directional isolation of 45 dB and operate over the frequency range 1-200 MHz. The system is tested using a focused PVDF transducer that is tuned for maximum sensitivity at 50 MHz, has a -6 dB lateral beamwidth of 70 microns and -6 dB depth-of-focus of 0.90 mm. This permits the practical use of sample volumes with dimensions 70 microns laterally by 90-900 microns axially. The PW HFD system can operate in duplex mode by either sharing the Doppler transducer or using a second PVDF transducer for imaging. Tests with string and capillary flow phantoms demonstrate that the PW HFD system is capable of detecting velocities on the order of the blood velocities found in the capillaries (0.5 mm/s) and arterioles (5 mm/s) with suitable velocity (30-300 microns/s) and temporal (15-100 ms) resolutions. In vivo measurements demonstrate that PW HFD can detect and measure blood velocities of less than 5 mm/s in arterioles and venules with diameters as small as 20 microns and 35 microns, respectively, using a sample volume of only 70 microns laterally by 150 microns axially. Preliminary experiments with high-frequency colour Doppler (HFCD) and high-frequency power Doppler (HFPD) imaging are also presented.

A 40-100 MHz B-scan ultrasound backscatter microscope for skin imaging.

There is a growing interest in high resolution, subsurface imaging of cutaneous tissues using higher frequency ultrasound, and several commercial systems have been developed recently which operate at 20 MHz. Some of the possible applications of higher frequency skin imaging include tumour staging, boundary definition, and studies of the response of tumours to therapy, investigations of inflammatory skin conditions such as psoriasis and eczema, and basic studies of skin aging, sun damage and the effects of irritants. Investigation of these areas is quite new, and the role of ultrasound skin imaging is continuing to evolve. Lateral resolution in the 20 MHz imaging systems ranges from 200 to 300 microns, which limits imaging applications to cutaneous structures which are relatively large in size. In this paper, a real-time ultrasound backscatter microscope (UBM) for skin imaging is described which operates in the 40-100 MHz range, providing axial resolution between 17 and 30 microns and lateral resolution between 33 and 94 microns. This improvement in resolution over current skin ultrasound systems should prove useful in determining the margins of small skin lesions, and in obtaining more precise, in vivo skin thickness measurements to characterize nonmalignant skin disease. Example images of normal skin, seborrhoeic keratosis and malignant melanoma illustrate the imaging potential of this system.

A 100 MHz B-scan ultrasound backscatter microscope.

The construction and operation of a 100 MHz B-mode ultrasound backscatter microscope are described. The powerful B-mode technique is extended into the domain of microscopy allowing the imaging of internal structure in living specimens on a microscopic scale. A frame rate of 5 frames per second is achieved which gives rapid feedback to the operator. Specially designed components of the scanner are described in detail, including the transducer, motion system and scan converter. An f/2 transducer is employed, leading to a scanner resolution of approximately 36 micron in both the lateral and axial directions. The benefits of such high resolution are demonstrated in preliminary images of multicellular spheroids and intact human ocular tissue.