Complete Breast MRI Response to Neoadjuvant Chemotherapy and Prediction of Pathologic Complete Response.

OBJECTIVE: To assess the negative predictive value (NPV) of breast MRI in detecting residual disease after neoadjuvant chemotherapy (NAC) in women with invasive breast cancer, overall and by tumor subtype. METHODS: An institutional review board approved retrospective study from January 2010 through December 2016 identified patients with invasive breast cancer who achieved complete MRI response to NAC, defined as the absence of residual enhancement in the tumor bed above background parenchymal enhancement. During the study period, it was our routine practice to assign a BI-RADS 1 or 2 assessment to these cases. The NPV was defined as the ability of a complete MRI response to predict pathologic complete response (pCR) at final surgical pathology. Statistical analyses were performed using a Fisher exact test. RESULTS: Among 244 patients who underwent MRI to assess NAC response, 38 (16%) were determined to have complete MRI response by the interpreting radiologist. Of these, 20/38 (53%) had pCR. Complete MRI response did not significantly predict pCR for the total group (P < 0.9). However, NPVs significantly varied by molecular subtype (P < 0.004). True negative MRIs by tumor subtype were 2/10 (20%) for hormone receptor (HR)+/HER2-, 3/10 (30%) for HR+/HER2+, 6/8 (75%) for HR-/HER+, and 9/10 (90%) for triple negative (TN) subtypes. Complete MRI response significantly predicted pCR for only the TN subtype (NPV 90%; P < 0.02). CONCLUSIONS: In patients with complete MRI response, 53% had pCR. While MRI lacks sufficient NPV to obviate the need for surgical excision, it may add prognostic value for certain molecular subtypes. The TN subtype demonstrated the highest NPV.

Pain sensitivity is inversely related to regional grey matter density in the brain.

Pain is a highly personal experience that varies substantially among individuals. In search of an anatomical correlate of pain sensitivity, we used voxel-based morphometry to investigate the relationship between grey matter density across the whole brain and interindividual differences in pain sensitivity in 116 healthy volunteers (62 women, 54 men). Structural magnetic resonance imaging (MRI) and psychophysical data from 10 previous functional MRI studies were used. Age, sex, unpleasantness ratings, scanner sequence, and sensory testing location were added to the model as covariates. Regression analysis of grey matter density across the whole brain and thermal pain intensity ratings at 49°C revealed a significant inverse relationship between pain sensitivity and grey matter density in bilateral regions of the posterior cingulate cortex, precuneus, intraparietal sulcus, and inferior parietal lobule. Unilateral regions of the left primary somatosensory cortex also exhibited this inverse relationship. No regions showed a positive relationship to pain sensitivity. These structural variations occurred in areas associated with the default mode network, attentional direction and shifting, as well as somatosensory processing. These findings underscore the potential importance of processes related to default mode thought and attention in shaping individual differences in pain sensitivity and indicate that pain sensitivity can potentially be predicted on the basis of brain structure.

The contribution of the putamen to sensory aspects of pain: insights from structural connectivity and brain lesions.

Cerebral cortical activity is heavily influenced by interactions with the basal ganglia. These interactions occur via cortico-basal ganglia-thalamo-cortical loops. The putamen is one of the major sites of cortical input into basal ganglia loops and is frequently activated during pain. This activity has been typically associated with the processing of pain-related motor responses. However, the potential contribution of putamen to the processing of sensory aspects of pain remains poorly characterized. In order to more directly determine if the putamen can contribute to sensory aspects of pain, nine individuals with lesions involving the putamen underwent both psychophysical and functional imaging assessment of perceived pain and pain-related brain activation. These individuals exhibited intact tactile thresholds, but reduced heat pain sensitivity and widespread reductions in pain-related cortical activity in comparison with 14 age-matched healthy subjects. Using magnetic resonance imaging to assess structural connectivity in healthy subjects, we show that portions of the putamen activated during pain are connected not only with cortical regions involved in sensory-motor processing, but also regions involved in attention, memory and affect. Such a framework may allow cognitive information to flow from these brain areas to the putamen where it may be used to influence how nociceptive information is processed. Taken together, these findings indicate that the putamen and the basal ganglia may contribute importantly to the shaping of an individual subjective sensory experience by utilizing internal cognitive information to influence activity of large areas of the cerebral cortex.

Psychological and sensory predictors of experimental thermal pain: a multifactorial model.

UNLABELLED: Although large interindividual differences in pain exist, the underlying factors that contribute to these variations remain poorly understood. Consequently, being able to accurately explain variability in pain ratings in terms of its contributing factors could provide insights into developing a better understanding of individual differences in pain experience. In the present investigation, we show that a significant portion of the variability in experimental heat pain ratings may be predicted using simple quantitative sensory testing and a series of psychological questionnaires including State Trait and Anxiety Inventory (STAI), Center for Epidemiologic Studies - Depression Scale (CES-D), and Positive and Negative Affect Schedule - Expanded form (PANAS-X). A factor analysis was used to reduce individual predictors into sets of composite predictive factors. A multifactorial model that was generated from these factors can reliably predict a significant amount of the variability in heat pain sensitivity ratings (r² = .537, P = .027). Moreover, individual variables including heat pain thresholds and self-assessment of pain sensitivity were found to be poor predictors of heat pain sensitivity. Taken together, these results suggest that a variety of factors underlie individual differences in pain experience and that a reliable model for predicting pain should be constructed from a combination of these factors. PERSPECTIVE: The present study provides a way to predict subjects' experimental heat pain sensitivity using a multifactorial model generated from a combination of sensory and psychological factors. Future application of such a model in the studies of clinical pain could potentially improve the quality of care provided for patients in pain.

Roles of the insular cortex in the modulation of pain: insights from brain lesions.

Subjective sensory experiences are constructed by the integration of afferent sensory information with information about the uniquely personal internal cognitive state. The insular cortex is anatomically positioned to serve as one potential interface between afferent processing mechanisms and more cognitively oriented modulatory systems. However, the role of the insular cortex in such modulatory processes remains poorly understood. Two individuals with extensive lesions to the insula were examined to better understand the contribution of this brain region to the generation of subjective sensory experiences. Despite substantial differences in the extent of the damage to the insular cortex, three findings were common to both individuals. First, both subjects had substantially higher pain intensity ratings of acute experimental noxious stimuli than age-matched control subjects. Second, when pain-related activation of the primary somatosensory cortex was examined during left- and right-sided stimulation, both individuals exhibited dramatically elevated activity of the primary somatosensory cortex ipsilateral to the lesioned insula in relation to healthy control subjects. Finally, both individuals retained the ability to evaluate pain despite substantial insular damage and no evidence of detectable insular activity. Together, these results indicate that the insula may be importantly involved in tuning cortical regions to appropriately use previous cognitive information during afferent processing. Finally, these data suggest that a subjectively available experience of pain can be instantiated by brain mechanisms that do not require the insular cortex.