Breast MRI during Neoadjuvant Chemotherapy: Lack of Background Parenchymal Enhancement Suppression and Inferior Treatment Response.

Background Suppression of background parenchymal enhancement (BPE) is commonly observed after neoadjuvant chemotherapy (NAC) at contrast-enhanced breast MRI. It was hypothesized that nonsuppressed BPE may be associated with inferior response to NAC. Purpose To investigate the relationship between lack of BPE suppression and pathologic response. Materials and Methods A retrospective review was performed for women with menopausal status data who were treated for breast cancer by one of 10 drug arms (standard NAC with or without experimental agents) between May 2010 and November 2016 in the Investigation of Serial Studies to Predict Your Therapeutic Response with Imaging and Molecular Analysis 2, or I-SPY 2 TRIAL (NCT01042379). Patients underwent MRI at four points: before treatment (T0), early treatment (T1), interregimen (T2), and before surgery (T3). BPE was quantitatively measured by using automated fibroglandular tissue segmentation. To test the hypothesis effectively, a subset of examinations with BPE with high-quality segmentation was selected. BPE change from T0 was defined as suppressed or nonsuppressed for each point. The Fisher exact test and the Z tests of proportions with Yates continuity correction were used to examine the relationship between BPE suppression and pathologic complete response (pCR) in hormone receptor (HR)-positive and HR-negative cohorts. Results A total of 3528 MRI scans from 882 patients (mean age, 48 years ± 10 [standard deviation]) were reviewed and the subset of patients with high-quality BPE segmentation was determined (T1, 433 patients; T2, 396 patients; T3, 380 patients). In the HR-positive cohort, an association between lack of BPE suppression and lower pCR rate was detected at T2 (nonsuppressed vs suppressed, 11.8% [six of 51] vs 28.9% [50 of 173]; difference, 17.1% [95% CI: 4.7, 29.5]; P = .02) and T3 (nonsuppressed vs suppressed, 5.3% [two of 38] vs 27.4% [48 of 175]; difference, 22.2% [95% CI: 10.9, 33.5]; P = .003). In the HR-negative cohort, patients with nonsuppressed BPE had lower estimated pCR rate at all points, but the P values for the association were all greater than .05. Conclusions In hormone receptor-positive breast cancer, lack of background parenchymal enhancement suppression may indicate inferior treatment response. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Philpotts in this issue.

A Comparison of Methods for High-Spatial-Resolution Diffusion-weighted Imaging in Breast MRI.

Background Diffusion-weighted imaging (DWI) shows promise in detecting and monitoring breast cancer, but standard spin-echo (SE) echo-planar DWI methods often have poor image quality and low spatial resolution. Proposed alternatives include readout-segmented (RS) echo-planar imaging and axially reformatted (AR)-simultaneous multislice (SMS) imaging. Purpose To compare the resolution and image quality of standard SE echo-planar imaging DWI with two high-spatial-resolution alternatives, RS echo-planar and AR-SMS imaging, for breast imaging. Materials and Methods In a prospective study (2016-2018), three 5-minute DWI protocols were acquired at 3.0 T, including standard SE echo-planar imaging, RS echo-planar imaging with five segments, and AR-SMS imaging with four times slice acceleration. Participants were women undergoing breast MRI either as part of a treatment response clinical trial or undergoing breast MRI for screening or suspected cancer. A commercial breast phantom was imaged for resolution comparison. Three breast radiologists reviewed images in random order, including clinical images indicating the lesion, images with b value of 800 sec/mm2, and apparent diffusion coefficient (ADC) maps from the three randomly labeled DWI methods. Readers measured the longest dimension and lesion-average ADC on three DWI methods, reported measurement confidence, and rated or ranked the quality of each image. The scores were fit to a linear mixed-effects model with intercepts for reader and subject. Results The smallest feature (1 mm) was only detectible in a phantom on images from AR-SMS DWI. Thirty lesions from 28 women (mean age, 50 years ± 13 [standard deviation]) were evaluated. On the five-point Likert scale for image quality, AR-SMS imaging scored 1.31 points higher than SE echo-planar imaging and 0.74 points higher than RS echo-planar imaging, whereas RS echo-planar imaging scored 0.57 points higher than SE echo-planar imaging (all P < .001). Conclusion The axially reformatted simultaneous multislice protocol was rated highest for image quality, followed by the readout-segmented echo-planar imaging protocol. Both were rated higher than the standard spin-echo echo-planar imaging. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Partridge in this issue.

Nyquist ghost correction of breast diffusion weighted imaging using referenceless methods.

PURPOSE: Correction of Nyquist ghosts for single-shot spin-echo EPI using the standard 3-line navigator often fails in breast DWI because of incomplete fat suppression, respiration, and greater B0 inhomogeneity. The purpose of this work is to compare the performance of the 3-line navigator with 4 data-driven methods termed "referenceless methods," including 2 previously proposed in literature, 1 introduced in this work, and finally a combination of all 3, in breast DWI. METHODS: Breast DWI was acquired for 41 patients with SS SE-EPI. Raw data was corrected offline with the standard 3-line navigator and 4 referenceless methods, which modeled the ghost as a linear phase error and minimized 3 unique cost functions as well as the median solution of all 3. Ghost levels were evaluated based on the signal intensity in the background region, defined by a mask auto-generated from a T1 -weighted anatomical image. Ghost intensity measurements were fit to a linear mixed model including ghost correction method and b-value as covariates. RESULTS: All 4 referenceless methods outperformed the standard 3-line navigator with statistical significance at all 4 b-values tested (b = 0, 100, 600, and 800 s/mm2 ). CONCLUSIONS: Referenceless methods provide a robust way to reduce Nyquist ghosts in breast DWI without the need for any additional calibration scan.

MR spectroscopy of breast cancer for assessing early treatment response: Results from the ACRIN 6657 MRS trial.

PURPOSE: To estimate the accuracy of predicting response to neoadjuvant chemotherapy (NACT) in patients with locally advanced breast cancer using MR spectroscopy (MRS) measurements made very early in treatment. MATERIALS AND METHODS: This prospective Health Insurance Portability and Accountability Act (HIPAA)-compliant protocol was approved by the American College of Radiology and local-site institutional review boards. One hundred nineteen women with invasive breast cancer of ≥3 cm undergoing NACT were enrolled between September 2007 and April 2010. MRS measurements of the concentration of choline-containing compounds ([tCho]) were performed before the first chemotherapy regimen (time point 1, TP1) and 20-96 h after the first cycle of treatment (TP2). The change in [tCho] was assessed for its ability to predict pathologic complete response (pCR) and radiologic response using the area under the receiver operating characteristic curve (AUC) and logistic regression models. RESULTS: Of the 119 subjects enrolled, only 29 cases (24%) with eight pCRs provided usable data for the primary analysis. Technical challenges in acquiring quantitative MRS data in a multi-site trial setting limited the capture of usable data. In this limited data set, the decrease in tCho from TP1 to TP2 had poor ability to predict either pCR (AUC = 0.53, 95% confidence interval [CI]: 0.27-0.79) or radiologic response (AUC = 0.51, 95% CI: 0.27-0.75). CONCLUSION: The technical difficulty of acquiring quantitative MRS data in a multi-site clinical trial setting led to a low yield of analyzable data, which was insufficient to accurately measure the ability of early MRS measurements to predict response to NACT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:290-302.

High-spatial- and high-temporal-resolution dynamic contrast-enhanced MR breast imaging with sweep imaging with Fourier transformation: a pilot study.

PURPOSE: To report the results of sweep imaging with Fourier transformation (SWIFT) magnetic resonance (MR) imaging for diagnostic breast imaging. MATERIALS AND METHODS: Informed consent was obtained from all participants under one of two institutional review board-approved, HIPAA-compliant protocols. Twelve female patients (age range, 19-54 years; mean age, 41.2 years) and eight normal control subjects (age range, 22-56 years; mean age, 43.2 years) enrolled and completed the study from January 28, 2011, to March 5, 2013. Patients had previous lesions that were Breast Imaging Reporting and Data System 4 and 5 based on mammography and/or ultrasonographic imaging. Contrast-enhanced SWIFT imaging was completed by using a 4-T research MR imaging system. Noncontrast studies were completed in the normal control subjects. One of two sized single-breast SWIFT-compatible transceiver coils was used for nine patients and five controls. Three patients and five control subjects used a SWIFT-compatible dual breast coil. Temporal resolution was 5.9-7.5 seconds. Spatial resolution was 1.00 mm isotropic, with later examinations at 0.67 mm isotropic, and dual breast at 1.00 mm or 0.75 mm isotropic resolution. RESULTS: Two nonblinded breast radiologists reported SWIFT image findings of normal breast tissue, benign fibroadenomas (six of six lesions), and malignant lesions (10 of 12 lesions) concordant with other imaging modalities and pathologic reports. Two lesions in two patients were not visualized because of coil field of view. The images yielded by SWIFT showed the presence and extent of known breast lesions. CONCLUSION: The SWIFT technique could become an important addition to breast imaging modalities because it provides high spatial resolution at all points during the dynamic contrast-enhanced examination.

Physician communication in the operating room.

In this study, communication research was conducted with multidisciplinary groups of operating-room physicians. Theoretical frameworks from intercultural communication and rhetoric were used to (a) measure latent cultural communication variables and (b) conduct communication training with the physicians. A six-step protocol guided the research with teams of physicians from different surgical specialties: anesthesiologists, general surgeons, and obstetrician-gynecologists (n = 85). Latent cultural communication variables were measured by surveys administered to physicians before and after completion of the protocol. The centerpiece of the 2-hour research protocol was an instructional session that informed the surgical physicians about rhetorical choices that support participatory communication. Post-training results demonstrated scores increased on communication variables that contribute to collaborative communication and teamwork among the physicians. This study expands health communication research through application of combined intercultural and rhetorical frameworks, and establishes new ways communication theory can contribute to medical education.

Repeatability of Respiratory Exchange Ratio Time Series Analysis.

Currently, there are few studies on the repeatability of a time series analysis of respiratory exchange ratio (RER) under the same conditions. This repeated-measures study compared 2 trials completed under the same conditions. After an 8-hour fast, subjects (7 male and 5 female) (mean ± SD) of age 27.3 ± 3.7 years, body weight of 71.8 ± 8.4 kg, percent body fat of 16.4 ± 8.1%, and peak oxygen uptake (V[Combining Dot Above]O2peak) of 46.0 ± 5.3 ml·kg·min completed a V[Combining Dot Above]O2peak test followed 7 days later by a cycle ergometer test at 30% of ventilatory threshold (VT) and 60% of VT for 15 minutes each. These tests were repeated again 7 days later. Paired t-tests revealed no significant differences between the tests for mean RER or sample entropy (SampEn) score at both intensities. The coefficients of variance were generally similar for the mean and SampEn of the RER. The intraclass correlation coefficient (ICC) values for the mean RER at 30% of VT were 1.00 and at 60% of VT were 0.92. The ICC values for the SampEn RER at 30% of VT were 0.81 and at 60% of VT were the lowest at 0.25. Bland-Altman plots demonstrated a measure of agreement between both methods. We demonstrated that RER measurements at 30 and 60% of VT are repeatable during steady-state cycle ergometery. Future research should determine if this finding is consistent with a larger sample size and different exercise intensities.

International society of sports nutrition position stand: coffee and sports performance.

Based on review and critical analysis of the literature regarding the contents and physiological effects of coffee related to physical and cognitive performance conducted by experts in the field and selected members of the International Society of Sports Nutrition (ISSN), the following conclusions represent the official Position of the Society:(1) Coffee is a complex matrix of hundreds of compounds. These are consumed with broad variability based upon serving size, bean type (e.g. common Arabica vs. Robusta), and brew method (water temperature, roasting method, grind size, time, and equipment).(2) Coffee's constituents, including but not limited to caffeine, have neuromuscular, antioxidant, endocrine, cognitive, and metabolic (e.g. glucose disposal and vasodilation) effects that impact exercise performance and recovery.(3) Coffee's physiologic effects are influenced by dose, timing, habituation to a small degree (to coffee or caffeine), nutrigenetics, and potentially by gut microbiota differences, sex, and training status.(4) Coffee and/or its components improve performance across a temporal range of activities from reaction time, through brief power exercises, and into the aerobic time frame in most but not all studies. These broad and varied effects have been demonstrated in men (mostly) and in women, with effects that can differ from caffeine ingestion, per se. More research is needed.(5) Optimal dosing and timing are approximately two to four cups (approximately 473-946 ml or 16-32 oz.) of typical hot-brewed or reconstituted instant coffee (depending on individual sensitivity and body size), providing a caffeine equivalent of 3-6 mg/kg (among other components such as chlorogenic acids at approximately 100-400 mg per cup) 60 min prior to exercise.(6) Coffee has a history of controversy regarding side effects but is generally considered safe and beneficial for healthy, exercising individuals in the dose range above.(7) Coffee can serve as a vehicle for other dietary supplements, and it can interact with nutrients in other foods.(8) A dearth of literature exists examining coffee-specific ergogenic and recovery effects, as well as variability in the operational definition of "coffee," making conclusions more challenging than when examining caffeine in its many other forms of delivery (capsules, energy drinks, "pre-workout" powders, gum, etc.).

Free radical signalling underlies inhibition of CaV3.2 T-type calcium channels by nitrous oxide in the pain pathway.

Nitrous oxide (N2O, laughing gas) has been used as an anaesthetic and analgesic for almost two centuries, but its cellular targets remain unclear. Here, we present a molecular mechanism of nitrous oxide's selective inhibition of CaV3.2 low-voltage-activated (T-type) calcium channels in pain pathways. Using site-directed mutagenesis and metal chelators such as diethylenetriamine pentaacetic acid and deferoxamine, we reveal that a unique histidine at position 191 of CaV3.2 participates in a critical metal binding site, which may in turn interact with N2O to produce reactive oxygen species (ROS). These free radicals are then likely to oxidize H191 of CaV3.2 in a localized metal-catalysed oxidation reaction. Evidence of hydrogen peroxide and free radical intermediates is given in that N2O inhibition of CaV3.2 channels is attenuated when H2O2 is neutralized by catalase. We also use the adrenochrome test as an indicator of ROS in vitro in the presence of N2O and iron. Ensuing in vivo studies indicate that mice lacking CaV3.2 channels display decreased analgesia to N2O in response to formalin-induced inflammatory pain. Furthermore, a superoxide dismutase and catalase mimetic, EUK-134, diminished pain responses to formalin in wild-type mice, but EUK-134 and N2O analgesia were not additive. This suggests that reduced ROS levels led to decreased inflammation, but without the presence of ROS, N2O was not able to provide additional analgesia. These findings reveal a novel mechanism of interaction between N2O and ion channels, furthering our understanding of this widely used analgesic in pain processing.

International society of sports nutrition position stand: caffeine and exercise performance.

Following critical evaluation of the available literature to date, The International Society of Sports Nutrition (ISSN) position regarding caffeine intake is as follows: 1. Supplementation with caffeine has been shown to acutely enhance various aspects of exercise performance in many but not all studies. Small to moderate benefits of caffeine use include, but are not limited to: muscular endurance, movement velocity and muscular strength, sprinting, jumping, and throwing performance, as well as a wide range of aerobic and anaerobic sport-specific actions. 2. Aerobic endurance appears to be the form of exercise with the most consistent moderate-to-large benefits from caffeine use, although the magnitude of its effects differs between individuals. 3. Caffeine has consistently been shown to improve exercise performance when consumed in doses of 3-6 mg/kg body mass. Minimal effective doses of caffeine currently remain unclear but they may be as low as 2 mg/kg body mass. Very high doses of caffeine (e.g. 9 mg/kg) are associated with a high incidence of side-effects and do not seem to be required to elicit an ergogenic effect. 4. The most commonly used timing of caffeine supplementation is 60 min pre-exercise. Optimal timing of caffeine ingestion likely depends on the source of caffeine. For example, as compared to caffeine capsules, caffeine chewing gums may require a shorter waiting time from consumption to the start of the exercise session. 5. Caffeine appears to improve physical performance in both trained and untrained individuals. 6. Inter-individual differences in sport and exercise performance as well as adverse effects on sleep or feelings of anxiety following caffeine ingestion may be attributed to genetic variation associated with caffeine metabolism, and physical and psychological response. Other factors such as habitual caffeine intake also may play a role in between-individual response variation. 7. Caffeine has been shown to be ergogenic for cognitive function, including attention and vigilance, in most individuals. 8. Caffeine may improve cognitive and physical performance in some individuals under conditions of sleep deprivation. 9. The use of caffeine in conjunction with endurance exercise in the heat and at altitude is well supported when dosages range from 3 to 6 mg/kg and 4-6 mg/kg, respectively. 10. Alternative sources of caffeine such as caffeinated chewing gum, mouth rinses, energy gels and chews have been shown to improve performance, primarily in aerobic exercise. 11. Energy drinks and pre-workout supplements containing caffeine have been demonstrated to enhance both anaerobic and aerobic performance.

A modeling study of T-type Ca2+ channel gating and modulation by L-cysteine in rat nociceptors.

L-cysteine (L-cys) increases the amplitude of T-type Ca(2+) currents in rat T-rich nociceptor-like dorsal root ganglia neurons. The modulation of T-type Ca(2+) channel gating by L-cys was studied by fitting Markov state models to whole-cell currents recorded from T-rich neurons. The best fitting model tested included three resting states and inactivation from the second resting state and the open state. Inactivation and the final opening step were voltage-independent, whereas transitions between the resting states and deactivation were voltage-dependent. The transition rates between the first two resting states were an order of magnitude faster than those between the second and third resting states, and the voltage-dependency of forward transitions through resting states was two to three times greater than for analogous backward transitions. Analysis with the best fitting model suggested that L-cys increases current amplitude mainly by increasing the transition rate from resting to open and decreasing the transition rate from open to inactivated. An additional model was developed that could account for the bi-exponential time course of recovery from inactivation of the currents and the high frequency of blank sweeps in single channel recordings. This model detected basically the same effects of L-cys on channel gating as the best fitting model.

Molecular mechanisms of lipoic acid modulation of T-type calcium channels in pain pathway.

Alpha-lipoic acid (1,2-dithiolane-3-pentanoic acid; lipoic acid) is an endogenous compound used to treat pain disorders in humans, but its mechanisms of analgesic action are not well understood. Here, we show that lipoic acid selectively inhibited native Ca(V)3.2 T-type calcium currents (T-currents) and diminished T-channel-dependent cellular excitability in acutely isolated rat sensory neurons. Lipoic acid locally injected into peripheral receptive fields of pain-sensing sensory neurons (nociceptors) in vivo decreased sensitivity to noxious thermal and mechanical stimuli in wild-type but not Ca(V)3.2 knock-out mice. Ensuing molecular studies demonstrated that lipoic acid inhibited recombinant Ca(V)3.2 channels heterologously expressed in human embryonic kidney 293 cells by oxidating specific thiol residues on the cytoplasmic face of the channel. This study provides the first mechanistic demonstration of a nociceptive ion channel modulation that may contribute to the documented analgesic properties of lipoic acid in vivo.

Mechanisms of inhibition of T-type calcium current in the reticular thalamic neurons by 1-octanol: implication of the protein kinase C pathway.

Recent studies indicate that T-type calcium channels (T-channels) in the thalamus are cellular targets for general anesthetics. Here, we recorded T-currents and underlying low-threshold calcium spikes from neurons of nucleus reticularis thalami (nRT) in brain slices from young rats and investigated the mechanisms of their modulation by an anesthetic alcohol, 1-octanol. We found that 1-octanol inhibited native T-currents at subanesthetic concentrations with an IC(50) of approximately 4 muM. In contrast, 1-octanol was up to 30-fold less potent in inhibiting recombinant Ca(V)3.3 T-channels heterologously expressed in human embryonic kidney cells. Inhibition of both native and recombinant T-currents was accompanied by a hyperpolarizing shift in steady-state inactivation, indicating that 1-octanol stabilized inactive states of the channel. To explore the mechanisms underlying higher 1-octanol potency in inhibiting native nRT T-currents, we tested the effect of the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) and PKC inhibitors. We found that PMA caused a modest increase of T-current, whereas the inactive PMA analog 4alpha-PMA failed to affect T-current in nRT neurons. In contrast, 12-(2-cyanoethyl)-6,7,12,13-tetrahydro-13-methyl-5-oxo-5H-indolo(2,3-a)pyrrolo(3,4-c)-carbazole (Go 6976), an inhibitor of calcium-dependent PKC, decreased baseline T-current amplitude in nRT cells and abolished the effects of subsequently applied 1-octanol. The effects of 1-octanol were also abolished by chelation of intracellular calcium ions with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Taken together, these results suggest that inhibition of calcium-dependent PKC signaling is a possible molecular substrate for modulation of T-channels in nRT neurons by 1-octanol.

Cell-specific alterations of T-type calcium current in painful diabetic neuropathy enhance excitability of sensory neurons.

Recent data indicate that T-type Ca2+ channels are amplifiers of peripheral pain signals, but their involvement in disorders of sensory neurons such as those associated with diabetes is poorly understood. To address this issue, we used a combination of behavioral, immunohistological, molecular, and electrophysiological studies in rats with streptozotocin (N-[methylnitrosocarbamoil]-D-glucosamine)-induced early diabetic neuropathy. We found that, in parallel with the development of diabetes-induced pain, T-type current density increased by twofold in medium-size cells from L4-L5 dorsal root ganglia (DRG) with a depolarizing shift in steady-state inactivation. This not only correlated closely with more prominent afterdepolarizing potentials (ADPs) but also increased cellular excitability manifested as a lower threshold for burst firing in diabetic than in control cells. T-type currents and ADPs were potently inhibited by nickel and enhanced by L-cysteine, suggesting that the Ca(V)3.2 T-type channel isoform was upregulated. Both control and diabetic DRG cells with ADPs stained positively for isolectin B4, but only diabetic cells responded robustly to capsaicin, suggesting enhanced nociceptive function. Because increased excitability of sensory neurons may result in such pathological perceptions of pain as hyperalgesia and allodynia, upregulation of T-type Ca2+ currents and enhanced Ca2+ entry into these cells could contribute to the development of symptoms in diabetic neuropathy.

Reducing agents sensitize C-type nociceptors by relieving high-affinity zinc inhibition of T-type calcium channels.

Recent studies have demonstrated an important role for T-type Ca2+ channels (T-channels) in controlling the excitability of peripheral pain-sensing neurons (nociceptors). However, the molecular mechanisms underlying the functions of T-channels in nociceptors are poorly understood. Here, we demonstrate that reducing agents as well as endogenous metal chelators sensitize C-type dorsal root ganglion nociceptors by chelating Zn2+ ions off specific extracellular histidine residues on Ca(v)3.2 T-channels, thus relieving tonic channel inhibition, enhancing Ca(v)3.2 currents, and lowering the threshold for nociceptor excitability in vitro and in vivo. Collectively, these findings describe a novel mechanism of nociceptor sensitization and firmly establish reducing agents, as well as Zn2+, Zn2+-chelating amino acids, and Zn2+-chelating proteins as endogenous modulators of Ca(v)3.2 and nociceptor excitability.

Molecular mechanisms of subtype-specific inhibition of neuronal T-type calcium channels by ascorbate.

T-type Ca2+ channels (T-channels) are involved in the control of neuronal excitability and their gating can be modulated by a variety of redox agents. Ascorbate is an endogenous redox agent that can function as both an anti- and pro-oxidant. Here, we show that ascorbate selectively inhibits native Ca(v)3.2 T-channels in peripheral and central neurons, as well as recombinant Ca(v)3.2 channels heterologously expressed in human embryonic kidney 293 cells, by initiating the metal-catalyzed oxidation of a specific, metal-binding histidine residue in domain 1 of the channel. Our biophysical experiments indicate that ascorbate reduces the availability of Ca(v)3.2 channels over a wide range of membrane potentials, and inhibits Ca(v)3.2-dependent low-threshold-Ca2+ spikes as well as burst-firing in reticular thalamic neurons at physiologically relevant concentrations. This study represents the first mechanistic demonstration of ion channel modulation by ascorbate, and suggests that ascorbate may function as an endogenous modulator of neuronal excitability.

MR Spectroscopy in the diagnosis and treatment of breast cancer.

In vivo proton magnetic resonance spectroscopy ((1)H MRS) is rapidly becoming useful as a clinical tool for diagnosing and characterizing breast cancers. Alterations of the levels of choline-containing metabolites are associated with malignancy. High-field MR scanners at 1.5 T, 3 T, 4 T, and 7 T have been used to evaluate the role of (1)H MRS measurements of total choline containing compounds in patients with breast cancer. This article will review clinical use of MRI/MRS in vivo. Newer developments in high field MR scanning and quantitative MRS may help breast imagers improve sensitivity and specificity in diagnosing and treating breast cancer.

The endogenous redox agent L-cysteine induces T-type Ca2+ channel-dependent sensitization of a novel subpopulation of rat peripheral nociceptors.

Recent studies have demonstrated a previously unrecognized contribution of T-type Ca2+ channels in peripheral sensory neurons to pain sensation (nociception). However, the cellular mechanisms underlying the functions of these channels in nociception are not known. Here, in both acutely dissociated and intact rat dorsal root ganglion neurons, we characterize a novel subpopulation of capsaicin- and isolectin B4-positive nociceptors that also expresses a high density of T-type Ca2+ currents. Using these "T-rich" cells as a model, we demonstrate that the endogenous reducing agent L-cysteine lowers the threshold for nociceptor excitability and induces burst firing by increasing the amplitude of T-type currents and shifting the gating parameters of T-type channels. These findings, which provide the first direct evidence of T-type Ca2+ channel involvement in the control of nociceptor excitability, suggest that endogenous T-type channel agonists may sensitize a unique subpopulation of peripheral nociceptors, consequently influencing pain processing under normal or pathological conditions.

Is there a role for T-type calcium channels in peripheral and central pain sensitization?

Following tissue injury, both peripheral and central sensory neurons can become hyperexcitable, or "sensitized." Sensitization can lead to long-term pathological changes in pain sensation. Because many chronic pain conditions are refractory to most currently available treatments, there is great interest in identifying molecular targets that contribute to the sensitization of sensory neurons. Among these, several classes of ion channels have emerged as potential targets. Recent in vitro and in vivo studies have demonstrated a role for T-type Ca2+ channels in sensory pathways and have suggested that these channels may contribute to pain processing and sensitization. Therefore, T-type channels may represent an opportunity for the development of novel pain therapeutics and may help to address an unmet medical need.

Imaging in breast cancer: Magnetic resonance spectroscopy.

A technique called in vivo magnetic resonance spectroscopy (MRS) can be performed along with magnetic resonance imaging (MRI) to obtain information about the chemical content of breast lesions. This information can be used for several clinical applications, such as monitoring the response to cancer therapies and improving the accuracy of lesion diagnosis. Initial MRS studies of breast cancer show promising results, and a growing number of research groups are incorporating the technique into their breast MRI protocols. This article introduces 1H-MRS of the breast, reviews the literature, discusses current methods and technical issues, and describes applications for treatment monitoring and lesion diagnosis.