QUANTITATIVE THREE DIMENSIONAL ELASTICITY IMAGING

Neoplastic tissue is typically highly vascularized, contains abnormal concentrations of extracellular proteins (e.g. collagen, proteoglycans) and has a high interstitial fluid pres- sure compared to most normal tissues. These changes result in an overall stiffening typical of most solid tumors. Elasticity Imaging (EI) is a technique which uses imaging systems to measure relative tissue deformation and thus noninvasively infer its mechanical stiffness. Stiffness is recovered from measured deformation by using an appropriate mathematical model and solving an inverse problem. The integration of EI with existing imaging modal- ities can improve their diagnostic and research capabilities. The aim of this work is to develop and evaluate techniques to image and quantify the mechanical properties of soft tissues in three dimensions (3D). To that end, this thesis presents and validates a method by which three dimensional ultrasound images can be used to image and quantify the shear modulus distribution of tissue mimicking phantoms. This work is presented to motivate and justify the use of this elasticity imaging technique in a clinical breast cancer screening study. The imaging methodologies discussed are intended to improve the specificity of mammography practices in general. During the development of these techniques, several issues concerning the accuracy and uniqueness of the result were elucidated. Two new algorithms for 3D EI are designed and characterized in this thesis. The first provides three dimensional motion estimates from ultrasound images of the deforming ma- terial. The novel features include finite element interpolation of the displacement field, inclusion of prior information and the ability to enforce physical constraints. The roles of regularization, mesh resolution and an incompressibility constraint on the accuracy of the measured deformation is quantified. The estimated signal to noise ratio of the measured displacement fields are approximately 1800, 21 and 41 for the axial, lateral and eleva- tional components, respectively. The second algorithm recovers the shear elastic modulus distribution of the deforming material by efficiently solving the three dimensional inverse problem as an optimization problem. This method utilizes finite element interpolations, the adjoint method to evaluate the gradient and a quasi-Newton BFGS method for optimiza- tion. Its novel features include the use of the adjoint method and TVD regularization with piece-wise constant interpolation. A source of non-uniqueness in this inverse problem is identified theoretically, demonstrated computationally, explained physically and overcome practically. Both algorithms were test on ultrasound data of independently characterized tissue mimicking phantoms. The recovered elastic modulus was in all cases within 35% of the reference elastic contrast. Finally, the preliminary application of these techniques to tomosynthesis images showed the feasiblity of imaging an elastic inclusion.

A Formal Semantics for Weak References

A weak reference is a reference to an object that is not followed by the pointer tracer when garbage collection is called. That is, a weak reference cannot prevent the object it references from being garbage collected. Weak references remain a troublesome programming feature largely because there is not an accepted, precise semantics that describes their behavior (in fact, we are not aware of any formalization of their semantics). The trouble is that weak references allow reachable objects to be garbage collected, therefore allowing garbage collection to influence the result of a program. Despite this difficulty, weak references continue to be used in practice for reasons related to efficient storage management, and are included in many popular programming languages (Standard ML, Haskell, OCaml, and Java). We give a formal semantics for a calculus called λweak that includes weak references and is derived from Morrisett, Felleisen, and Harper’s λgc. λgc formalizes the notion of garbage collection by means of a rewrite rule. Such a formalization is required to precisely characterize the semantics of weak references. However, the inclusion of a garbage-collection rewrite-rule in a language with weak references introduces non-deterministic evaluation, even if the parameter-passing mechanism is deterministic (call-by-value in our case). This raises the question of confluence for our rewrite system. We discuss natural restrictions under which our rewrite system is confluent, thus guaranteeing uniqueness of program result. We define conditions that allow other garbage collection algorithms to co-exist with our semantics of weak references. We also introduce a polymorphic type system to prove the absence of erroneous program behavior (i.e., the absence of “stuck evaluation”) and a corresponding type inference algorithm. We prove the type system sound and the inference algorithm sound and complete.

Towards Formalizing Java's Weak References

Weak references provide the programmer with limited control over the process of memory management. By using them, a programmer can make decisions based on previous actions that are taken by the garbage collector. Although this is often helpful, the outcome of a program using weak references is less predictable due to the nondeterminism they introduce in program evaluation. It is therefore desirable to have a framework of formal tools to reason about weak references and programs that use them. We present several calculi that formalize various aspects of weak references, inspired by their implementation in Java. We provide a calculus to model multiple levels of non-strong references, where a different garbage collection policy is applied to each level. We consider different collection policies such as eager collection and lazy collection. Similar to the way they are implemented in Java, we give the semantics of eager collection to weak references and the semantics of lazy collection to soft references. Moreover, we condition garbage collection on the availability of time and space resources. While time constraints are used in order to restrict garbage collection, space constraints are used in order to trigger it. Finalizers are a problematic feature in Java, especially when they interact with weak references. We provide a calculus to model finalizer evaluation. Since finalizers have little meaning in a language without side-effect, we introduce a limited form of side effect into the calculus. We discuss determinism and the separate notion of uniqueness of (evaluation) outcome. We show that in our calculus, finalizer evaluation does not affect uniqueness of outcome.