Training deep neural networks with noisy clinical labels: toward accurate detection of prostate cancer in US data.

PURPOSE: Ultrasound is the standard-of-care to guide the systematic biopsy of the prostate. During the biopsy procedure, up to 12 biopsy cores are randomly sampled from six zones within the prostate, where the histopathology of those cores is used to determine the presence and grade of the cancer. Histopathology reports only provide statistical information on the presence of cancer and do not normally contain fine-grain information of cancer distribution within each core. This limitation hinders the development of machine learning models to detect the presence of cancer in ultrasound so that biopsy can be more targeted to highly suspicious prostate regions. METHODS: In this paper, we tackle this challenge in the form of training with noisy labels derived from histopathology. Noisy labels often result in the model overfitting to the training data, hence limiting its generalizability. To avoid overfitting, we focus on the generalization of the features of the model and present an iterative data label refinement algorithm to amend the labels gradually. We simultaneously train two classifiers, with the same structure, and automatically stop the training when we observe any sign of overfitting. Then, we use a confident learning approach to clean the data labels and continue with the training. This process is iteratively applied to the training data and labels until convergence. RESULTS: We illustrate the performance of the proposed method by classifying prostate cancer using a dataset of ultrasound images from 353 biopsy cores obtained from 90 patients. We achieve area under the curve, sensitivity, specificity, and accuracy of 0.73, 0.80, 0.63, and 0.69, respectively. CONCLUSION: Our approach is able to provide clinicians with a visualization of regions that likely contain cancerous tissue to obtain more accurate biopsy samples. The results demonstrate that our proposed method produces superior accuracy compared to the state-of-the-art methods.

Towards targeted ultrasound-guided prostate biopsy by incorporating model and label uncertainty in cancer detection.

PURPOSE: Systematic prostate biopsy is widely used for cancer diagnosis. The procedure is blind to underlying prostate tissue micro-structure; hence, it can lead to a high rate of false negatives. Development of a machine-learning model that can reliably identify suspicious cancer regions is highly desirable. However, the models proposed to-date do not consider the uncertainty present in their output or the data to benefit clinical decision making for targeting biopsy. METHODS: We propose a deep network for improved detection of prostate cancer in systematic biopsy considering both the label and model uncertainty. The architecture of our model is based on U-Net, trained with temporal enhanced ultrasound (TeUS) data. We estimate cancer detection uncertainty using test-time augmentation and test-time dropout. We then use uncertainty metrics to report the cancer probability for regions with high confidence to help the clinical decision making during the biopsy procedure. RESULTS: Experiments for prostate cancer classification includes data from 183 prostate biopsy cores of 41 patients. We achieve an area under the curve, sensitivity, specificity and balanced accuracy of 0.79, 0.78, 0.71 and 0.75, respectively. CONCLUSION: Our key contribution is to automatically estimate model and label uncertainty towards enabling targeted ultrasound-guided prostate biopsy. We anticipate that such information about uncertainty can decrease the number of unnecessary biopsy with a higher rate of cancer yield.

Multiple instance learning combined with label invariant synthetic data for guiding systematic prostate biopsy: a feasibility study.

PURPOSE: Ultrasound imaging is routinely used in prostate biopsy, which involves obtaining prostate tissue samples using a systematic, yet, non-targeted approach. This approach is blinded to individual patient intraprostatic pathology, and unfortunately, has a high rate of false negatives. METHODS: In this paper, we propose a deep network for improved detection of prostate cancer in systematic biopsy. We address several challenges associated with training such network: (1) Statistical labels: Since biopsy core's pathology report only represents a statistical distribution of cancer within the core, we use multiple instance learning (MIL) networks to enable learning from ultrasound image regions associated with those data; (2) Limited labels: The number of biopsy cores are limited to at most 12 per patient. As a result, the number of samples available for training a deep network is limited. We alleviate this issue by effectively combining Independent Conditional Variational Auto Encoders (ICVAE) with MIL. We train ICVAE to learn label-invariant features of RF data, which is subsequently used to generate synthetic data for improved training of the MIL network. RESULTS: Our in vivo study includes data from 339 prostate biopsy cores of 70 patients. We achieve an area under the curve, sensitivity, specificity, and balanced accuracy of 0.68, 0.77, 0.55 and 0.66, respectively. CONCLUSION: The proposed approach is generic and can be applied to several other scenarios where unlabeled data and noisy labels in training samples are present.

Reference-based source separation method for identification of brain regions involved in a reference state from intracerebral EEG.

In this paper, we present a fast method to extract the sources related to interictal epileptiform state. The method is based on general eigenvalue decomposition using two correlation matrices during: 1) periods including interictal epileptiform discharges (IED) as a reference activation model and 2) periods excluding IEDs or abnormal physiological signals as background activity. After extracting the most similar sources to the reference or IED state, IED regions are estimated by using multiobjective optimization. The method is evaluated using both realistic simulated data and actual intracerebral electroencephalography recordings of patients suffering from focal epilepsy. These patients are seizure-free after the resective surgery. Quantitative comparisons of the proposed IED regions with the visually inspected ictal onset zones by the epileptologist and another method of identification of IED regions reveal good performance.