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Definitions

• the present invention relates, generally, to ultrasound focusing and, more
• the relative phases of drive signals delivered to each transducer element may be adjusted based on the distance of each transducer element from the focal zone. Generally, an average speed of sound is used to approximate the speed at which the acoustic energy passes through tissue and to predict the location of the focal zone.
• the present invention provides systems and methods for predicting the effects on an ultrasound beam (e.g., aberrations) when traversing tissue (such as a human skull) having a complex structure, shape, density, and/ or thickness using a precedent- based approach.
• tissue such as a human skull
• an acquired training set or a library including various features of the tissue (e.g., a skull) and acoustic aberrations (e.g., phase shifts, time delays, intensities, etc.) resulting from travel of an acoustic beam through the tissue is first created.
• the method further includes computationally predicting the reliability of the predicted first aberrations.
• the measurements may include data obtained from the images of the first anatomical regions, acoustic reflections from the first anatomical regions, and/or acoustic spectral activities at the first anatomical regions.
• the characteristics include anatomical characteristics, sonication parameters, information of the transducer elements, and/or characteristics of a measurement system.
• the sonication parameters may include a frequency, an intensity and/or a phase associated with each one of the ultrasound waves.
• the information of the transducer elements may include a size, a shape, a location and/or an orientation of each transducer element.
• the information is extracted by transfer learning, autoencoding, principal component analysis and/or scale-invariant feature transform.
• the characteristics may further include the ultrasound aberrations predicted using a model.
• computational prediction step may include using the predictor to predict the first aberrations based at least in part on similarities between the first values of the characteristics associated with the first anatomical regions and the second values of the characteristics associated with the second anatomical regions.
• the similarity is determined based at least in part on pointwise similarity between the first and second series of measurements.
• the second ultrasound aberrations are acquired using an aberration measurement and/or an aberration prediction.
• one or more of the second values of the characteristics associated with the second anatomical regions are redundant.
• the second series of measurements may include two or more redundant values that correspond to different second ultrasound aberrations and/or different preprocessing.
• Preprocessing the first and/or second series of measurements may be carried out in multiple steps; one or more of the steps used to preprocess the first series of measurements may ⁇ be the same as one or more of the steps used to preprocess the second series of measurements.
• the second series of measurements may include data derived from the second series of images of the second anatomical regions, and the preprocessing may include determining rotation angles of the second series of images of the second anatomical regions prior to determining characteristics thereof.
• the method includes acquiring the third series of images of the second anatomical regions based at least in part on the determined rotation angles. The third series of images of the second anatomical regions is acquired using resampling and/or interpolation of the second series of images of the second anatomical regions.
• the predictor may include a neural network.
• the characteristics of the first anatomical regions are determined based at least in part on angles between orientations of the first anatomical regions and beam paths of the ultrasound waves traveling therethrough.
• the method may further include determining the accuracy of the predicted first aberrations of the ultrasound waves based on a reliability estimation of the prediction, a similarity measure between the first series and a second series of measurements, and/or a prediction success associated with the second series of measurements.
• the invention in another aspect, relates to an ultrasound system including an ultrasound transducer having multiple transducer elements; a measuring system for acquiring the first series of measurements of multiple first anatomical regions through which the ultrasound waves emitted from the transducer elements will travel; and a processor.
• the measuring system may include an imager for acquiring the first series of images of the first anatomical regions and/or an acoustic detector for detecting acoustic reflections from the first anatomical regions and/or acoustic spectral activities at the first anatomical regions
• the imager includes a magnetic resonance imaging device, a computer tomography device, a positron emission tomography device, a single-photon emission computed tomography device, and/or an ultrasonography device.
• the invention in another aspect, relates to a method of operating an ultrasound transducer having multiple transducer elements.
• the method includes (a) acquiring a series of one or more measurements of multiple anatomical regions through winch ultrasound waves emitted from the transducer elements will travel; (b) for each of the anatomical regions, determining the values of multiple characteristics based at least in part on the series of measurements; (c) computationally predicting the aberrations of the ultrasound waves traveling through the anatomical regions by using the values as input to a predictor that has been computationally trained to predict ultrasound aberrations based on the values of the
• FIGS. 1 OA- IOC depict the relationship between the degree to which predictions deviate from actual measurements and various types of input images utilized in a convolutional neural network in accordance with various embodiments;
• FIGS. 11 A-l ID depict the relationship between the degree to which predictions deviate from actual measurements and a layer number in a convolutional neural network having multiple layers (from which skull features are extracted and provided to a random-forest model) in accordance with various embodiments;
• FIG. 1 illustrates an exemplary ultrasound therapy system 100 for focusing ultrasound onto a target region 101 within a patient's brain through the skull.
• the system 100 includes a phased array 102 of transducer elements 104, a beamformer 106 driving the phased array 102, a controller 108 in communication with the beamformer 106, and a frequency generator 110 providing an input electronic signal to the beamformer 106.
• the system further includes an imager 1 12, such as a magnetic resonance imaging (MRI) device, a computer tomography (CT) device, a positron emission tomography (PET) device, a single-photon emission computed tomography (SPECT) device, an optical camera or an ultrasonography device, for acquiring information of the target region 101 and its surrounding region and/or determining anatomical characteristics of the skull 114 of a patient's head 1 16.
• MRI magnetic resonance imaging
• CT computer tomography
• PET positron emission tomography
• SPECT single-photon emission computed tomography
• ultrasonography device for acquiring information of the target region 101 and its surrounding region and/or determining anatomical characteristics of the skull 114 of a patient's head 1 16.
• the transducer array 102 is coupled to the beamformer 106, which drives the individual transducer elements 104 so that they collectively produce a focused ultrasonic beam or field at the target region 101.
• the beamformer 106 may contain n driver circuits, each including or consisting of an amplifier 118 and a phase delay circuit 120; drive circuit drives one of the transducer elements 104.
• the beamformer 106 receives a radio frequency (RF) input signal, typically in the range from 0.1 MHz to 10 MHz, from the frequency generator 110, which may, for example, be a Model DS345 generator available from Stanford Research Systems.
• RF radio frequency
• the input signal may be split into n channels for the n amplifiers 118 and delay circuits 120 of the beamformer 106.
• the frequency generator 110 is integrated with the beamformer 106.
• the radio frequency generator 110 and the beamformer 106 are configured to drive the individual transducer elements 104 of the transducer array 102 at the same frequency, but at different phases and/or different amplitudes.
• the transducer array 102 is divided into multiple sub-regions each including a one- or two- dimensional array (i.e., a row or a matrix) of transducer elements 104.
• the sub-regions may be separately controllable, i.e., they are each capable of emitting ultrasound waves at amplitudes, frequencies, and/or phases that are independent of the amplitudes, frequencies and/or phases of the other sub-regions.
• the computation is based on detailed information about the characteristics (e.g., structure, thickness, density, etc.) of the skull 4 and their effects on propagation of acoustic energy. Such information may be obtained from the imaging system 112 as further described below.
• Image acquisition may be three-dimensional or, alternatively, the imaging sy stem 1 12 may provide a set of two-dimensional images suitable for reconstructing a three-dimensional image of the skull 114 from which the anatomical characteristics (e.g., thicknesses and densities) can be inferred.
• Image-manipulation functionality may be
• each transducer element is driven with a phase that is determined based on, for example, the location of the transducer element and the target region as well as acoustic properties of media located between the transducer element and the target region.
• the objective is to cause the beams from all active transducers to converge in phase at the focus. Because the acoustic properties of the bone tissue (e.g., a skull) are significantly different from those of the soft tissue, the presence of the bone tissue along the beam path may result in significant aberrations (e.g., phase shifts and/or time delays) to the acoustic beam.
• the aberration effects (such as phase shifts, time delays, etc.) on the ultrasound beam when traversing the skull 114 or other parts of the body are estimated using a precedent-based approach as depicted generically in FIG. 2,
• a training set including various known skull features (such as the structure, shape, density, and/or thickness) and aberrations experienced by the ultrasound waves when traveling through the skull 1 14 is created.
• the skull features are characterized based on images acquired using the imager 112. For example, referring to FIG.
• aberrations of the ultrasound waves caused by the skull 1 14 are measured using a sensor (e.g., a hydrophone) 310 placed at the target region 306.
• the sensor 310 may first detect the ultrasound pulses traversing fluid between the transducer 102 and the target region. After the skull is introduced in close proximity to the transducer (such that the transducer, target and skull are immersed in a water bath), the sensor 310 detects ultrasound pulses traversing each skull patch 304. Acoustic aberrations (which correspond to volumetric changes in the acoustic field, such as a phase shift and/or time delay) introduced as the pulses pass through the skull can then be determined based on the sensor measurements and stored as data of the training set.
• the aberration measurement in the presence of the skull is performed multiple times at several target locations across the skull to increase the size of the training set. In addition, each measurement may be repeated one or more times to reduce noise.
• the performance of the updated inference function is considered satisfactory and the updated inference function is stored in the system memory for later retrieval to predict aberrations in ultrasound waves traversing various skull features (step 208). If, however, the deviation between the estimated and measured aberrations is above the predetermined threshold, parameters associated with the machine learning approach are further adjusted; the evaluation process is repeated until the deviation between the estimated and measured aberrations is below the threshold or satisfies another suitable criterion.
• the measured phase shifts (which may or may not be unwrapped) may be analyzed and corrected before being used as a training set.
• the measured values may be corrected by removing the shift. This shift may be found, for example, by a phasor diagram of the measured ultrasound waves transmitted from the transducer elements that provide low acoustic amplitudes in fluid measurements only.
• the size of the imaging volumes 502 is fixed for all samples.
• the location of the imaging volume 502 along the z axis may or may not be fixed for all samples.
• the image volume 502 is taken with a smaller range of locations along the z axis around the skull center of mass to reduce input sparsity. in that case, information regarding the location of the imaging volume 502 along the z axis (i.e., the direction beam propagation) may be provided to the machine- learning model as well.
• a center plane 508 passing through the COM and perpendicular to the beam path 506 can be defined.
• the center plane 508 divides the skull volume 504 into an upper region 5 0 and a lower region 512 and is defined in the figure as the x-y plane in the Cartesian coordinate system.
• the locations of the COMs of the upper and lower regions 5 0, 512 are determined.
• FIGS. 5D and 5E depict an approach for computationally determining the rotation angle ⁇ associated with each skull patch.
• the rotation angle ⁇ is determined based on the x and j components of the projection vector v pro .
• the images acquired using the imager 112 have different resolutions for different orientations. This may cause the skull volumes 504 to have different boundary shapes.
• Various approaches may be implemented to process the images so as to accurately acquire the skull features based on a consistent boundary. For example, augmented data based on additional images where the resolutions are different may be used cooperatively with the images originally acquired.
• various known approaches may be applied to smooth the boundaries of the skull volumes.
• augmentation data is extracted from the same, originally acquired images but with a reduced resolution (e.g., by ignoring at least a portion of the data).
• the spatial size and resolution of the image slice are defined (e.g., a slice having a region of 14 x 14 mm in the x-y plane may be represented by 8 x 8 pixels); each pixel is associated with a ray at the matching x and y coordinates and with z from the element 104 to target.
• Each ray is represented by points along it with a predefined spacing, and each point along a ray is provided with a value taken from the original images or its derivatives (e.g. the CT image intensity in Haunsfield unit, or the image intensity after using a smoothing filter or the image gradient value) at the relevant location.
• This technique can also be applied to images acquired using different imagers.
• beam properties e.g., a phase shift or an intensity
• a neural network or any other learning model
• This approach provides the neural network with a much larger training set than that obtainable using actual measurements.
• the model results may be augmented with noise (which may be skull- patch dependent) before being used as labels in the learning process in order to simulate real measurements obtained in clinical practice.
• the learning model is adapted to the actual measurements, e.g., by fine-tuning.
• FIG. 8F depicts another regression result of a different skull. Again, the phase shifts generally negatively correlate to the skull thickness and data from the four skull measurements 840-846 collapses.
• some or all data of the training set may be used to predict aberrations of the ultrasound beam when traversing the skull.
• transducer elements 104 are activated in a single measurement; their receiving data is split into a training set that includes 900 elements and a test set that includes only 100 elements (e.g., selecting every 10 th element).
• the test set may additionally or alternatively include data received in other measurement(s) and/or using other transducer elements.
• the test set includes only measurements performed with skulls that are not used in any of the measurements in the training set. While multiple data sets may be acquired in multiple measurements, the skull patches used in the test set should not overlap with those used in the training set.
• a single, specific feature may be first compared to multiple features; the similarity measure of the specific feature may then be computed as a percentage of the cases in the multiple features whose similanty measures are above a predefined threshold corresponding to the specific feature.
• FIGS. 11 A-l ID illustrate this approach in practice, depicting the relationship between observed deviations (including MSED and Focus) and a layer number (which is fully connected) in the convolutional neural network (which has multiple layers) from which the features are extracted and used in a random forest model.
• FIGS. 12A-12F illustrate the relationship between the deviations (including MSED, Focus, and Wfocus) and the number of trees used in the random-forest model.

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