Safety of high-dose-rate brachytherapy in patients with prostate cancer and inflammatory bowel disease: A case series.

Introduction: Inflammatory bowel disease (IBD) is a relative contraindication to external beam radiation therapy (EBRT) for prostate cancer patients due to fear of increased risk of gastrointestinal (GI) toxicity. High-dose-rate (HDR) brachytherapy, capable of minimizing radiation dose to surrounding tissues, is a feasible alternative. Given limited data, this study examined the safety profile of HDR brachytherapy in this setting. Material and methods: We conducted a retrospective review of patients with localized prostate cancer and IBD treated with HDR brachytherapy at the University of California San Francisco (UCSF), between 2010 and 2022. Eligibility criteria included biopsy-proven prostate cancer, no distant metastases, absence of prior pelvic radiotherapy, IBD diagnosis, and at least one follow-up visit post-treatment. Results: Eleven patients were included, with a median follow-up of 28.7 months. The median dose administered was 2700 cGy (range, 1500-3150 cGy) over 2 fractions (range, 1-3 fractions). Two patients also received EBRT. Rectal spacers (SpaceOAR) were applied in seven patients. All patients experienced acute genitourinary (GU) toxicity, ten of which were grade 1 and one was grade 2. Eight patients experienced late grade 1 GU toxicity, and three patients had late grade 2 GU toxicity. GI toxicities were similarly low-grade, with six grade 1 acute toxicity, no grade 2 or higher acute toxicity, six grade 1 late toxicity, and one late grade 2 GI toxicity. No grade 3 or higher acute or late GI or GU toxicities were reported. Conclusions: HDR brachytherapy appears to be a safe and tolerable treatment modality for patients with prostate cancer and IBD, with minimal acute and late GI and GU toxicity. These findings warrant multi-institutional validation due to small sample size.

Reducing the Environmental Impact of Health Care Conferences: A Study of Emissions and Practical Solutions.

PURPOSE: We aimed to examine the impact of different conference formats (in-person, virtual, and hybrid) of the ASCO conference on greenhouse gas (GHG) emissions and to recommend sustainable options for future conferences. MATERIALS AND METHODS: This study used data on the number of attendees, their departure locations, and the type of attendance (in-person v virtual) provided by ASCO between 2019 and 2022. The GHG emissions resulting from air and ground travel, remote connectivity, conference space utilization, hotel stays, distributed conference materials, and electricity use were estimated for each year. Emissions were stratified by attendee country of origin, type of attendance, and year. Simulations were conducted to evaluate how changes in conference size, location, and format impact emissions, as well as estimate the resulting mitigations from adopting the proposed changes. RESULTS: The highest estimated GHG emissions, calculated in carbon dioxide equivalents (CO2e), were associated with the 2019 in-person conference (37,251 metric tons of CO2e). Although international attendees had the largest contribution to emissions in all years (>50%), location optimization models, which selected conference locations that most minimized GHG emissions, yielded only minimal reductions (approximately 3%). Simulations examining changes to the conference format, location, and attendance percentage suggested that hub-and-spoke, where multiple conference locations are selected by global region, or hybrid models, with both in-person and virtual components, are likely to cause the largest drops in emissions (up to 86%). CONCLUSION: Using historical conference data, this study identifies key aspects that can be modified to reduce emissions and consequently promote more sustainable and equitable conference attendance. Hybrid conferences may be the best solution to maintain the networking opportunities provided by conferences while balancing out their environmental footprint.

Effectiveness of virtual reality in relieving anxiety and controlling hemodynamics during oral surgery under local anesthesia: A prospective randomized comparative study.

It was the aim of the study to evaluate the contribution of a relaxing immersive experience with virtual reality (VR) goggles in reducing patient anxiety related to wisdom tooth extraction under local anesthesia. A prospective randomized comparative study in consecutive patients scheduled for bilateral wisdom tooth extraction under local anesthesia was carried out between March and December 2022. Both sides were operated upon in the same surgery, but on one side VR goggles were applied (VR), while on the other they were not (noVR). Anxiety was evaluated both subjectively (State-Trait Anxiety Inventory [STAI] and visual analogue scale [VAS]) and objectively (measuring heart rate, blood pressure [BP] and blood oxygen saturation) before (T1) and after each surgical step (T2VR and T2noVR). The study sample consisted of 27 patients: 9 men and 18 women, with an average age of 25.8 ± 6.5 years (range: 18-43). Anxiety as assessed by the STAI and VAS decreased from T1 to T2 (p < 0.001 and p < 0.001, respectively), although to a similar degree regardless of whether VR was used or not. Heart rate showed significant differences influenced by RV exposure (p = 0.013): it increased +2.5 ± 8.8 bpm in the control group and decreased -2.22 ± 7.55 bpm with VR (p = 0.013). Both minimum and maximum BP after surgery were significantly higher in the noVR group (p = 0.002 and p = 0.040, respectively). Regarding minimum BP, VR proved more effective among male patients (p = 0.057) and on starting the procedure using VR (p = 0.055). The results provided evidence of meaningful control of the hemodynamic variables, but less predictable performance in the subjective evaluation of anxiety.

Multi-institutional Development and External Validation of a Machine Learning Model for the Prediction of Distant Metastasis in Patients Treated by Salvage Radiotherapy for Biochemical Failure After Radical Prostatectomy.

BACKGROUND: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy (SRT) being the only curative option. In 2016, Tendulkar et al. (Contemporary update of a multi-institutional predictive nomogram for salvage radiotherapy after radical prostatectomy. J Clin Oncol 2016;34:3648-54) published a nomogram to predict distant metastasis in a cohort of patients treated with SRT with pre-SRT prostate-specific antigen (PSA) of 0.5 ng/ml after radical prostatectomy. In modern practice, SRT is delivered at lower PSA values. OBJECTIVE: To train and externally validate a machine learning model to predict the risk of distant metastasis at 5 yr in a contemporary cohort of patients receiving SRT. DESIGN, SETTING, AND PARTICIPANTS: We trained a machine learning model on data from 2418 patients treated with SRT at one institution, with a median PSA value of 0.27 ng/ml. External validation was done in 475 patients treated at two different institutions. Patients with cM1, pN1, or pT4 disease were excluded, as were patients with PSA >2 ng/ml or PSA 0, and patients with radiation dose <60 or ≥80 Gy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Model performance was assessed using calibration and time-dependent area under the receiver operating curve (tAUC). RESULTS AND LIMITATIONS: Our model had better calibration and showed improved discrimination (tAUC = 0.72) compared with the Tendulkar model (tAUC = 0.60, p < 0.001). The main limitations of this study are its retrospective design and lack of validation on patients who received hormone therapy. CONCLUSIONS: The updated model can be used to provide more individualized risk assessments to patients treated with SRT at low PSA values, improving decision-making. PATIENT SUMMARY: Up to 40% of patients with prostate cancer may develop biochemical recurrence after surgery, with salvage radiation therapy as the only potentially curative option. We trained and validated a machine learning model using clinical and surgical data to predict a patient's risk of distant metastasis at 5 yr after treatment. Our model outperformed the reference tool and can improve clinical decision-making by providing more personalized risk assessment.

Safety of high-dose rate (HDR) brachytherapy for patients with prostate cancer and history of prior chemoradiation for rectal cancer: A case series.

PURPOSE: A history of prior pelvic radiation therapy (RT) for rectal cancer is a relative contraindication for definitive RT for prostate cancer. High-dose-rate (HDR) brachytherapy can significantly limit the dose to surrounding tissues compared to external beam RT. However, there is limited data surrounding its safety in patients with prior pelvic RT. METHODS AND MATERIALS: A retrospective chart review was performed at the University of California, San Francisco to identify patients diagnosed with prostate cancer with a history of pelvic RT for rectal cancer who were treated with high-dose-rate brachytherapy (HDR-BT) between 2006 and 2022. Inclusion criteria were biopsy-confirmed prostate cancer with no evidence of distant disease on clinical examination or imaging, and at least one post-treatment clinic appointment. RESULTS: Seven patients were treated with salvage HDR-BT at a median interval of 17.7 years after RT for rectal cancer. HDR-BT doses included 3600 cGy in six fractions (n = 5), 2700 cGy in 2 fractions (n=1), or 2800 cGy in four fractions (n = 1). There was no acute grade ≥2 gastrointestinal toxicity, and 1 patient developed late grade 2 rectal bleeding. Two patients developed acute grade 2 genitourinary toxicity consisting of urinary frequency and urgency, which persisted through long-term follow up. At a median follow up of 29.5 months after HDR brachytherapy, one patient developed regional and distant failure, and another had seminal vesicle recurrence. CONCLUSIONS: HDR-BT is a safe treatment for patients with prostate cancer who previously received RT for rectal cancer. Further studies are needed to better characterize the long-term toxicity of HDR-RT in this population.

Hypofractionation Adoption in Prostate Cancer Radiotherapy: Results of an International Survey.

PURPOSE: Hypofractionation is noninferior to conventional fractionation in the treatment of localized prostate cancer. Using results from the European Society of Radiation Oncology's (ESTRO) Global Impact of Radiotherapy in Oncology (GIRO) initiative survey on hypofractionation, this study identifies rates of adoption, facilitating factors, and barriers to adoption of hypofractionation in prostate cancer across World Bank income groups. MATERIALS AND METHODS: The ESTRO-GIRO initiative administered an international, anonymous, electronic survey to radiation oncologists from 2018 to 2019. Physician demographics, clinical practice characteristics, and hypofractionation regimen use (if any) for several prostate cancer scenarios were collected. Responders were asked about specific justifications and barriers to adopting hypofractionation, and responses were stratified by World Bank income group. Multivariate logistic regression models were used to analyze variables associated with hypofractionation preference. RESULTS: A total of 1,157 physician responses were included. Most respondents (60%) were from high-income countries (HICs). In the curative setting, hypofractionation was most often preferred in low- and intermediate-risk prostate cancers, with 52% and 47% of respondents reporting hypofractionation use in ≥50% of patients, respectively. These rates drop to 35% and 20% in high-risk prostate cancer and where pelvic irradiation is indicated. Most respondents (89%) preferred hypofractionation in the palliative setting. Overall, respondents from upper-middle-income countries and lower-middle- and low-income countries were significantly less likely to prefer hypofractionation than those from HICs (P < .001). The most frequently cited justification and barrier were availability of published evidence and fear of worse late toxicity, respectively. CONCLUSION: Hypofractionation preference varies by indication and World Bank income group, with greater acceptance among providers in HICs for all indications. These results provide a basis for targeted interventions to increase provider acceptance of this treatment modality.

Evaluating the Environmental Impact of Radiation Therapy Using Life Cycle Assessments: A Critical Review.

Concurrent increases in global cancer burden and the climate crisis pose an unprecedented threat to public health and human well-being. Today, the health care sector greatly contributes to greenhouse gas emissions, with the future demand for health care services expected to rise. Life cycle assessment (LCA) is an internationally standardized tool that analyzes the inputs and outputs of products, processes, and systems to quantify associated environmental impacts. This critical review explains the use of LCA methodology and outlines its application to external beam radiation therapy (EBRT) with the aim of providing a robust methodology to quantify the environmental impact of radiation therapy care practices today. The steps of an LCA are outlined and explained as defined by the International Organization for Standardization (ISO 14040 and 14044) guidelines: (1) definition of the goal and scope of the LCA, (2) inventory analysis, (3) impact assessment, and (4) interpretation. The existing LCA framework and its methodology is described and applied to the field of radiation oncology. The goal and scope of its application to EBRT is the evaluation of the environmental impact of a single EBRT treatment course within a radiation oncology department. The methodology for data collection via mapping of the resources used (inputs) and the end-of-life processes (outputs) associated with EBRT is explained, with subsequent explanation of the LCA analysis steps. Finally, the importance of appropriate sensitivity analysis and the interpretations that can be drawn from LCA results are reviewed. This critical review of LCA protocol provides and evaluates a methodological framework to scientifically establish baseline environmental performance measurements within a health care setting and assists in identifying targets for emissions mitigation. Future LCAs in the field of radiation oncology and across medical specialties will be crucial in informing best practices for equitable and sustainable care in a changing climate.

Development and External Validation of a Machine Learning Model for Prediction of Lymph Node Metastasis in Patients with Prostate Cancer.

BACKGROUND: Pelvic lymph node dissection (PLND) is the gold standard for diagnosis of lymph node involvement (LNI) in patients with prostate cancer. The Roach formula, Memorial Sloan Kettering Cancer Center (MSKCC) calculator, and Briganti 2012 nomogram are elegant and simple traditional tools used to estimate the risk of LNI and select patients for PLND. OBJECTIVE: To determine whether machine learning (ML) can improve patient selection and outperform currently available tools for predicting LNI using similar readily available clinicopathologic variables. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data for patients treated with surgery and PLND between 1990 and 2020 in two academic institutions were used. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We trained three models (two logistic regression models and one gradient-boosted trees-based model [XGBoost]) on data provided from one institution (n = 20267) with age, prostate-specific antigen (PSA) levels, clinical T stage, percentage positive cores, and Gleason scores as inputs. We externally validated these models using data from another institution (n = 1322) and compared their performance to that of the traditional models using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA). RESULTS AND LIMITATIONS: LNI was present in 2563 patients (11.9%) overall, and in 119 patients (9%) in the validation data set. XGBoost had the best performance among all the models. On external validation, its AUC outperformed that of the Roach formula by 0.08 (95% confidence interval [CI] 0.042-0.12), the MSKCC nomogram by 0.05 (95% CI 0.016-0.070), and the Briganti nomogram by 0.03 (95% CI 0.0092-0.051; all p < 0.05). It also had better calibration and clinical utility in terms of net benefit on DCA across relevant clinical thresholds. The main limitation of the study is its retrospective design. CONCLUSIONS: Taking all measures of performance together, ML using standard clinicopathologic variables outperforms traditional tools in predicting LNI. PATIENT SUMMARY: Determining the risk of cancer spread to the lymph nodes in patients with prostate cancer allows surgeons to perform lymph node dissection only in patients who need it and avoid the side effects of the procedure in those who do not. In this study, we used machine learning to develop a new calculator to predict the risk of lymph node involvement that outperformed traditional tools currently used by oncologists.

Outcomes of salvage high dose-rate brachytherapy with or without pelvic external beam radiotherapy in patients with palpable local recurrence of prostate cancer after radical prostatectomy.

PURPOSE: This study aims to evaluate the outcomes and toxicities in patients with palpable local recurrence of prostate cancer after radical prostatectomy (RP), who were treated with salvage high dose-rate brachytherapy (HDR-BT) with or without pelvic external beam radiotherapy (EBRT). METHODS: This retrospective review included patients with palpable local recurrence of prostate cancer after RP who underwent salvage HDR-BT at a single institution between 2002 and 2020. HDR-BT regimens included 950 cGy x 2 (N = 4) or 1500 cGy x 1 (N = 2) combined with EBRT; or monotherapy with 950 cGy x 4 (N = 1) or 800 cGy x 2 (N = 1). Toxicity was graded according to CTCAE Version 5.0. RESULTS: A total of 8 patients were included. Median follow-up was 49 months (range: 9-223 months). Median age at time of salvage brachytherapy was 68 years (range: 59-85 years). Seven out of 8 patients were alive at last follow-up. There have been no locoregional recurrences. Three patients developed distant metastatic disease. One patient developed acute grade 3 urinary obstruction requiring catheterization, which lasted for 1 day postbrachytherapy. One patient developed late grade 3 urinary incontinence 18 months after brachytherapy. There were no other grade 2+ toxicities. CONCLUSIONS: This study demonstrates the safety and efficacy of salvage HDR-BT in the setting of palpable local recurrence of prostate cancer after RP, with durable locoregional control and acceptable rates of toxicity. HDR-BT should be further explored as an option for dose-escalated salvage radiotherapy after prior radical prostatectomy.

A case of cetuximab-induced radiation recall skin dermatitis and review of the literature.

Radiation recall presents as an acute inflammatory reaction triggered by systemic therapy, usually chemotherapy, and is typically limited to an area that was previously irradiated. Radiation recall reactions are generally self-limiting and most commonly occur in the skin. Many systemic agents have been described to elicit a radiation recall reaction, but the exact pathogenesis is largely unknown. Here, we describe the first reported case of radiation recall dermatitis following cetuximab. While cetuximab is associated with other skin reactions, oncologists should not exclude radiation recall dermatitis as a potential complication of cetuximab infusion in patients with prior radiation, and special attention should be paid to the pattern of skin changes both in terms of location and chronology.

Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET.

Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans have higher sensitivity and specificity for detecting lymph nodes or metastatic disease relative to conventional imaging in prostate cancer staging. Since its FDA approval and incorporation into treatment guidelines, the use of PSMA PET has increased in patients undergoing initial staging, those with recurrence after initial definitive treatment, and patients with metastatic disease. Although the early detection of metastatic lesions is changing disease management, it is unclear whether this impact on management translates into clinical benefit. This review will summarize evidence pertaining to the change in patient management due to PSMA PET use and will discuss the implications of PSMA PET on treatment decisions in prostate cancer, particularly in the settings of biochemical recurrence and metachronous oligometastatic disease.

Prevalence of Cosmetic Procedures among Lebanese Women.

Lebanese women have been portrayed as conceited and obsessed with physical appearance and its beautification through cosmetic procedures. Despite the pervasiveness of this notion, no formal studies have been conducted to assess the true prevalence of cosmetic procedures among Lebanese women. Additionally, no data exist to elucidate trends in popularity of cosmetic procedures over time. A cross-sectional study was conducted across Lebanese universities where surveys were distributed to women aged 18-31 years to estimate the prevalence of surgical, noninvasive, and dental cosmetic procedures in young Lebanese women. The collected survey data were analyzed using the Statistical Package for the Social Sciences (SPSS). In a sample of 877 women, 44% reported having undergone at least one cosmetic procedure in their lifetime. The most popular procedures performed were laser hair removal (32%), teeth whitening (14%), and rhinoplasty (9.3%). The obtained results revealed an increasing prevalence of cosmetic procedures, mirroring global trends. A variety of factors have contributed to the increasing popularity of cosmetic procedures, namely, higher availability, better affordability, and wider social acceptance over time. (SKINmed. 2022;20:422-427).

Non-Pharmacological Treatments of Psoriasis in Persian Medicine a Narrative Review.

Psoriasis is a chronic disease that has no definitive cure. In this review study, the main sources of Persian Medicine (PM) such as the Canon of Medicine (by Avicenna) and Al-Havi (by Rhazes) were assessed to identify non-pharmacological treatments for psoriasis. Several treatments that are recommended for this disease include nutritional advice, lifestyle modifications, and manipulation therapy such as wet cupping (Hijamah), leech therapy, and phlebotomy (Fasd). These recommendations may help to prevent recurrence and be useful in improving psoriasis. The efficacy of PM recommendations to improve psoriasis should be evaluated in future studies.

Bacterial bloodstream infections and patterns of resistance in patients with haematological malignancies at a tertiary centre in Lebanon over 10 years.

OBJECTIVES: Bacterial bloodstream infections (BSIs) with resistant pathogens in patients with haematological malignancies are rising due to increased use of novel chemotherapeutic agents and prophylactic antibiotics. Our goal was to understand the epidemiology and resistance patterns of bacterial pathogens in patients with haematological malignancies to help tailor empirical antibiotics and to limit resistance. METHODS: This was a retrospective chart review looking at bacterial BSI episodes between 2007-2017 in patients previously diagnosed with haematological malignancy at a tertiary-care centre in Lebanon. RESULTS: Among 165 hospitalised patients with haematological malignancy and bacterial BSI over 10 years, Gram-negative bacteria (GNB) caused 65.0% of all episodes, with the most common pathogens being Escherichia coli (45.6%), 79.6% of which were ESBL-producers, Pseudomonas aeruginosa (7.5%) and Acinetobacter baumannii (4.0%). The majority of the organisms (61.0%) were multidrug-resistant (MDR), with ANC < 100 neutrophils/µL (OR = 0.12, 95% CI 0.03-0.54) identified as an independent marker for increased multidrug resistance. The risk factors associated with increased mortality included recent use of amikacin (p<0.001) and infections with organisms resistant to amikacin (p<0.001) or ciprofloxacin (p=0.04). Our results reflect a persistent pattern of Gram-negative predominance with E. coli remaining the most common isolated pathogen in bacterial BSIs in patients with haematological malignancies. The relative frequency of GNB to Gram-positive bacteria remains similar to our data from 2007. CONCLUSION: The persistent divergence between worldwide data and the results observed in our centre and the increasing rates of MDR pathogens emphasise the importance of tailoring empirical antimicrobial therapy according to the centre's epidemiology.

Prevalence of methicillin resistance and superantigenic toxins in Staphylococcus aureus strains isolated from patients with cancer.

BACKGROUND: This study aimed to determine the frequency of methicillin-resistant Staphylococcus aureus (MRSA), antibiotic resistance patterns, superantigenic toxins profile, and clonality of this pathogen in patients with cancer. RESULTS: In total, 79 (25.7%) isolates were confirmed as Staphylococcus species, from which 38 (48.1%) isolates were S. aureus, and 29 (76.3%) isolates were confirmed as MRSA. The highest resistance in MRSA strains was seen against ciprofloxacin (86.2%) and erythromycin (82.8%). Teicoplanin, and linezolid were the most effective antibiotics. From all MRSA isolates, 3 strains (10.3%) were resistant to vancomycin with minimum inhibitory concentration values of 128 µg/ml. The prevalence of superantigenic toxins genes was as follows: pvl (10.5%), tsst-1 (36.8%), etA (23.7%), and etB (23.7%). The t14870 spa type with frequency of 39.5% was the most prevalent clone type circulating in the cancer patients. CONCLUSIONS: This study showed the circulating of spa t14870 as the most predominant MRSA clone in cancer patients of southwest Iran. Also, a diverse antibiotic resistance pattern and toxin profiles were seen among MRSA isolates.

Retrospective study of the incidence of portal vein thrombosis after splenectomy in hematological disorders: Risk factors and clinical presentation.

OBJECTIVE: Portal vein thrombosis (PVT) has been described as a rare complication after splenectomy. PVT associated risk factors after splenectomy in hematological disorders are poorly recognized. The aim of this study was to assess the prevalence and risk factors of PVT incidence in splenectomized patients. METHODS: One hundred twelve splenectomized patients with various hematologic diseases between 2008 and 2018 were enrolled in this study. Diagnosis was confirmed by Doppler ultrasonography (DUSG) and risk factors for PVT were sought based on the comparison of clinical and laboratory features between patients without and with PVT. RESULT: PVT was diagnosed in 4 (3.57%) patients in spite of receiving antiplatelet therapy. Patients with PVT were ß-thalassemia major (n = 2) and ß-thalassemia intermedia (n = 2). ß-thalassemia patients had a 3.5 times higher odds for PVT (95% CI: 2.41-5.33). No significant differences between patients with and without PVT in terms of age, gender and laboratory features were found. CONCLUSION: According to our data, ß-thalassemia, especially intermediate form, may be a risk factor for PVT and it can occur in spite of receiving antiplatelet therapy. Given that ß-thalassemia patients are at risk, early PVT detection may be useful for reduction of fatal PVT complication in splenectomized patients.

Efficacy of nebulized L-epinephrine for treatment of croup: a randomized, double-blind study.

The objective of this study was to compare the effect of L-epinephrine plus dexamethasone vs. dexamethasone for treatment of croup in children. A randomized, double-blind clinical trial was implemented on 174 patients with croup, aged from 6 months to 6 years, and admitted to the Amir Kabir Pediatric Hospital (Arak, Iran). After randomized allocation, patients were administered dexamethasone, and then, they received either saline or L-epinephrine. Westley croup scores, heart rate, respiratory rate, and blood pressure were recorded every half an hour for a total of 120 min. There was a significant difference in mean of croup scores between two groups (P < 0.009). In addition, a significant difference was seen on mean of heart rate between two groups (P < 0.026). Our results showed a considerable difference in reduction of velocity of croup scores in patients who received nebulized L-epinephrine compared to patients who received placebo.

T1- and T2-based MRI measures of diffuse gray matter and white matter damage in patients with multiple sclerosis.

Magnetic resonance imaging (MRI) has emerged as a powerful noninvasive tool to assist in the diagnosis and monitoring of multiple sclerosis (MS). In addition, investigators have used MRI metrics as supportive outcome measures to explore drug efficacy in clinical trials. Conventional MRI surrogates provide information at the macroscopic level but lack sensitivity and specificity in identifying the full extent of underlying MS pathology. They also show relatively weak relationships to clinical status such as predictive strength for clinical change. Advanced MRI techniques involving quantitative measures of diffuse damage in normal appearing (NA) white matter (WM) and gray matter (GM) may help in resolving this apparent clinical MRI paradox. T2 hypointensity has been described in the GM of patients with MS and has been linked to physical disability, cognitive dysfunction, and brain atrophy. While this T2 hypointensity is thought to represent iron deposition, this awaits pathologic confirmation. Advanced MRI measures of iron deposition such as R2, R2*, R2' relaxometry, 3T imaging and other new approaches are beginning to be applied to studies of MS and should yield interesting information. Both T1 and T2 relaxometry have a role in detecting damage in NA brain tissue that escapes detection by conventional MRI lesion measures. For example, T2 mapping may allow an assessment of myelin content in NAWM. In this review, we will focus on MRI advances in the last 10 years pertaining to T1 and T2 measures of diffuse GM and WM damage.