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We present a new laboratory setup for photoacoustic, transmission ultrasound and reflection ultrasound tomography. The system is based on a pair of independently rotating hemisphere segments on which are mounted acoustic transmitters and detectors. The interchangeability of the elements, as well as the ability to fully customise the acquisition protocol, allows for a considerable amount of flexibility in testing out different imaging approaches in both 2D and 3D. The current focus is the development of laser-induced ultrasound (LIUS) transmitters for use in tomographic imaging. We propose a transmitter design tuned for speed-of-sound mapping with a 1MHz centred response.

We present a 'hybrid' imaging approach which can image both light absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a computed tomography (CT) photoacoustic imager. The ultrasound transmission measurement method uses a strong optical absorber of small cross-section placed in the path of the light illuminating the sample. This absorber, which we call a passive element acts as a source of ultrasound. The interaction of ultrasound with the sample can be measured in transmission, using the same ultrasound detector used for photoacoustics. Such measurements are made at various angles around the sample in a CT approach. Images of the ultrasound propagation parameters, attenuation and speed of sound, can be reconstructed by inversion of a measurement model. We validate the method on specially designed phantoms and biological specimens. The obtained images are quantitative in terms of the shape, size, location, and acoustic properties of the examined heterogeneities. (C) 2010 Optical Society of America

Photoacoustic (PA) or optoacoustic (OA) imaging combines the high (blood) contrast to light with the high-resolution of ultrasound. The method can visualize vascularization deep inside tissue. Of late there is interest in PA imaging of synovial joints which are expected to be associated with increased vascularization in the event of rheumatoid arthritis (RA). We here describe our approach in investigating the application of the PA technique in arthritis. We are developing a CT-geometry version PA finger imager, intended for early clinical assessment of the method. The imager uses two curved array ultrasound detectors each with 64 elements with central frequencies 1.5 and 7.5 MHz respectively, stacked above each other. Both cover approximately 180 degrees of the circle. Illumination is provided with a multiple of optical fiber bundles coupled to a laser-OPO system. Ultrasound imaging is also possible with the system, since the curved arrays are each provided with 12 or 8 ultrasound pulsers. We have investigated systematically imaging of finger vasculature in healthy volunteers using an earlier laboratory prototype. In this paper we present finger imaging results of a patient diagnosed with rheumatoid arthritis.

Photoacoustic (optoacoustic) imaging can visualize vasculature deep in tissue using the high contrast of hemoglobin to light, with the high-resolution possible with ultrasound detection. Since angiogenesis, one of the hallmarks of cancer, leads to increased vascularity, photoacoustics holds promise in imaging breast cancer as shown in proof-of-principle studies. Here for the first time, we investigate if there are specific photoacoustic appearances of breast malignancies which can be related to the tumor vascularity, using an upgraded research imaging system, the Twente Photoacoustic Mammoscope. In addition to comparisons with x-ray and ultrasound images, in subsets of cases the photoacoustic images were compared with MR images and with vascular staining in histopathology. We were able to identify lesions in suspect breasts at the expected locations in 28 of 29 cases. We discovered generally three types of photoacoustic appearances reminiscent of contrast enhancement types reported in MR imaging of breast malignancies and first insights were gained into the relationship with tumor vascularity.

We present PAM, the Photoacoustic Mammoscope developed at the University of Twente, intended for initial retrospective clinical studies on subjects with breast tumours. A parallel plate geometry has been adopted and the breast will be gently compressed between a glass plate and a flat ultrasound detector matrix. Pulsed light (5 ns) from an Nd:YAG laser will impinge the breast through the glass plate in regions of interest; an appropriate number of the 590 elements of the detector matrix will be activated in succession to record photoacoustic signals. Three-dimensional image reconstruction employs a delay-and-sum beamforming algorithm. We discuss various instrumental aspects and the proposed imaging protocol. Performance studies of the ultrasound detector are presented in terms of sensitivity, frequency response and resolution. Details of the patient–instrument interface are provided. Finally some imaging results on well-characterized breast tissue phantoms with embedded tumour simulating inserts are shown.

Current imaging modalities are often not able to detect early stages of breast cancer with high imaging contrast. Visualizing malignancy-associated increased hemoglobin concentrations might improve breast cancer diagnosis. Photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound resolution, which makes it potentially ideal for breast imaging. The Twente Photoacoustic Mammoscope (PAM) has been designed specifically for this purpose. Based on a successful pilot study in 2007, a large clinical study using PAM has been started in December 2010. PAM uses a pulsed Q-switched Nd:YAG laser at 1064 nm to illuminate a region of interest on the breast. Photoacoustic signals are detected with a 1MHz, unfocused ultrasound detector array. Three dimensional data are reconstructed using an acoustic backprojection algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study, the goal was to optimize the visualization of malignancies. We performed sixteen technically acceptable measurements on confined breast malignancies. In the reconstructed volumes of all malignancies, a confined high contrast region could be identified at the expected lesion depth. After ten successful measurements, the illumination area was increased and the fluence was substantially decreased. This caused a further significant increase in PAM lesion contrast.

Purpose: Worldwide, every year more than 1,300,000 women are diagnosed with breast cancer and annually, about 450,000 women die from the disease [1]. However, the current practice of imaging the breast for the detection and diagnosis of cancer suffers from shortcomings [2]. The interactions of the probe energy—whether X‐rays, magnetic field, or ultrasound (US)—with a tumor are not sufficiently specific or sensitive compared with non‐ pathological tissue. This results in occurrences of false positives and false negatives, which lead to psychological and physical morbidity and mortality. Furthermore, though X‐ray mammography is the gold standard imaging modality, X‐rays are carcinogenic. Ultrasound and MRI are restricted in their use to being secondary procedures owing to low sensitivity (US), poor specificity (MRI), and high‐expense (MRI). There is thus a requirement for a technique that is relatively harmless and has the potential to detect the presence of carcinoma in a manner that is more specific and reliable than inspection of morphologic and anatomic changes. Methods Photoacoustic imaging has much potential in detecting the presence of a carcinoma based on the optical absorption contrast manifested by the tumor compared to healthy tissue. This higher absorption is due to the presence of blood contents in the enhanced vascularization associated with the growth and spread of cancer. In PA, short pulses of light are used to illuminate the tissue: absorption induces heating followed by rapid thermal expansion. This generates US waves that propagate through tissue, to be detected by acoustic transducers positioned at the surface. The time‐of‐flight (TOF), amplitude and duration of acoustic pulses recorded on the tissue surface possess information regarding the location, absorption, and dimensions of the source. By recording signals in a 2‐D grid of detector positions, a 3‐D reconstruction of the absorber is possible. The advantage of this approach compared with purely optical imaging is that the spatial resolution is superior because of the low scattering experienced by the US during propagation in soft tissue. In the Biomedical Photonic Imaging Group (BMPI) of the University of Twente (UT) we have worked to develop photoacoustic imaging for breast imaging [3]. In 2007, the BMPI group reported their first results of NIR photoacoustic imaging of breast cancer in human subjects: in 4 of 5 cases of suspect breasts higher photoacoustic contrast associated was observed [4]. Results: In December 2010, a new clinical study has been started at the Centre for Breast Care of the Medisch Spectrum Twente in Oldenzaal. In this study, a number of patients will be measured within a period of 1.5 years. Patients are measured within the normal diagnostic path at the Centre for Mammacare, in between the ultrasound investigation and the ultrasound guided biopsy. The study can be divided into three phases and for each phase patients are included based on the suspiciousness of their lesion. In the Phase 1 of the study, the focus is on a small number of patients with lesions that are highly suspicious for malignancy. The goal of this part of the study is to optimize the imaging methods for the visualization of malignancies. At the time of going to press Phase 1 has been successfully completed. Ten technically acceptable measurements have been performed all of breasts highly suspect for malignancy [5]. The photoacoustic images have been compared with conventional imaging methods such as X‐ray imaging, ultrasound imaging and in some cases Magnetic Resonance Imaging. Conclusions These results confirm the conclusions of the 2007 study: that NIR photoacoustic imaging has potential in the diagnosis of breast cancer. On‐going work involves imaging patients in the subsequent phases. In phase 2 of the study, a large number of patients with lesions that are suspicious for malignancy are measured in order to define the photoacoustic markers that are indicative for the presence of a malignancy. In the last phase of the study, the absence of those photoacoustic malignancy markers will be verified in subjects with either healthy breast tissue or benign lesions.

Worldwide, yearly about 450,000 women die from the consequences of breast cancer. Current imaging modalities are not optimal in discriminating benign from malignant tissue. Visualizing the malignancy-associated increased hemoglobin concentration might significantly improve early diagnosis of breast cancer. Since photoacoustic imaging can visualize hemoglobin in tissue with optical contrast and ultrasound-like resolution, it is potentially an ideal method for early breast cancer imaging. The Twente Photoacoustic Mammoscope (PAM) has been developed specifically for breast imaging. Recently, a large clinical study has been started in the Medisch Spectrum Twente in Oldenzaal using PAM. In PAM, the breast is slightly compressed between a window for laser light illumination and a flat array ultrasound detector. The measurements are performed using a Q-switched Nd:YAG laser, pulsed at 1064 nm and a 1 MHz unfocused ultrasound detector array. Three-dimensional data are reconstructed using a delay and sum reconstruction algorithm. Those reconstructed images are compared with conventional imaging and histopathology. In the first phase of the study 12 patients with a malignant lesion and 2 patients with a benign cyst have been measured. The results are used to guide developments in photoacoustic mammography in order to pave the way towards an optimal technique for early diagnosis of breast cancer.

We present a 'hybrid' imaging system, which can image both optical absorption properties and acoustic transmission properties of an object in a two-dimensional slice using a computed tomography photoacoustic imager. The ultrasound transmission measurement method uses a strong absorber of light which is placed in the path of the light illuminating the sample. This acts as a source of ultrasound, whose interaction with the sample can be measured at the far-end of the sample using the same ultrasound detector used for photoacoustics. Such measurements are made at various angles around the sample in a computerized tomography approach. The ultrasound transients at the multi-element detector at all projections are analyzed for both times-of-arrival and amplitude. Using a fan-beam projection reconstruction algorithm we obtain hybrid images of optical absorption, speed-of-sound and acoustic attenuation. We validate the method on an appropriate phantom

Photoacoustic imaging is based on detecting laser pulse induced ultrasound transients from absorbing structures in tissue. The technique combines the advantages of a high optical absorption exhibited by tumors for example with the high resolution possible with ultrasound. A conventional photoacoustic imager operating in a CT geometry comprises a light source, an ultrasound detector array and a coupling medium usually water between the subject under investigation and detector. The imaging protocol usually consists of obtaining projections at angles around the subject. Recently we reported a method of measuring the local speed-of-sound variations by the addition of an absorber to the conventional imager, arranged between the light source and subject. This generates an ultrasound signal which interacts with the subject which can then be detected at the far-end by the detector. This allows the measurement of the integrated speed-of-sound (SOS) at projections around the subject leading to the formation of SOS images. In this article we discuss further analysis of the ultrasound obtained at projections to obtain images of the acoustic attenuation as well. In addition conventional photoacoustic images of the subject are also formed. The principle is demonstrated on well-characterized phantoms and we discuss the potential applications of this technique.

Breast cancer dominates cancers in females. This burden on society and the room for improvements in the current practice of mammography have been stimuli for developing new modalities like photoacoustic mammography. At the University of Twente (UT), an instrument had been developed aimed at performing limited area scans on the human breast. This instrument is called the Twente Photoacoustic Mammoscope (PAM). The PAM is based on generating laser-induced ultrasound from absorbing structures in the breast. The heart of the instrument is a flat PVDF based detector matrix comprising 590 active elements. We show the performance characteristics of the ultrasound detector. The exciting source is an Nd:YAG laser operating at 1064 nm with 5 ns pulses. A study protocol was designed to explore the feasibility of using the PAM to detect cancer in the breasts of patients. The protocol was executed at the Medisch Spectrum Twente by using the mammoscope to obtain photoacoustic region-of-interest (ROI) images of the suspect/symptomatic breasts. We compare the photoacoustic images obtained with x-ray mammograms and ultrasound images. We show photoacoustic images of ROI in one case where we attribute high intensity regions to tumor vascularization.

The Twente Photoacoustic Mammoscope (PAM) is based on generating laser-induced ultrasound from absorbing structures in the breast. The heart of the instrument is a flat PVDF based detector matrix comprising 590 active elements. The exciting source is an Nd:YAG laser operating at 1064 nm with 5 ns pulses. The instrument is built around a hospital bed. A study protocol was designed to explore the feasibility of using the photoacoustic technique as embodied in PAM to detect cancer in the breasts of patients with suspect/symptomatic breasts. The protocol was approved by a Medical Ethics testing committee and the instrument approved for laser and electrical safety. The protocol was executed at the Medisch Spectrum Twente by using the mammoscope to obtain photoacoustic region-of-interest (ROI) images of the suspect/symptomatic breasts. We report on one case and compare the photoacoustic images obtained with x-ray mammograms and ultrasound images.