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Placental function is vitally important, but placental assessment is limited by current imaging methods in vivo. The goal of this study is to determine if ferumoxytol-enhanced MR studies might be used to depict placental structure during pregnancy.Ten pregnant women were referred for MRI evaluation of abnormal placentation. The study group was composed five of these patients whose placentas were normal at pathology. MR studies consisted of pre-contrast SSFSE (single-shot fast spin-echo), SSFP (steady-state free procession), diffusion, and ferumoxytol-enhanced acquisitions. The post-contrast sequences were compared to pre-contrast SSFSE, SSFP, and diffusion acquisitions for features of correspondence. MR images were also compared to histopathology for anatomic landmarks including the three-ring pattern of the functional vascular exchange unit (the placentone) created by this central cavity surrounded by a ring of clustered villi, and an outer ring of dispersed villi corresponding to the maternal venous outflow channel. The measured sizes of these features on MR were compared to reported sizes.Post-ferumoxytol images showed enhancement of the maternal blood within the placenta, notably the intervillous space and the myometrial vessels. The unenhanced fetal vessels were most visible on the MinIP (minimum intensity projection) images; the enhanced maternal vessels were most visible on the MIP (maximum intensity projection) images. Composite MIP/MinIP images show the relation of maternal and fetal circulations. The signal intensities replicate the relative contributions from enhanced maternal blood and unenhanced chorionic villi.Ferumoxytol-enhanced MR imaging can depict the internal anatomy of the placenta in vivo of clarity and detail. This could represent a new diagnostic approach to placental disorders.

Chronic liver disease (CLD) is a large and ever-growing problem in both the US and world health care systems. While histologic analysis through liver biopsy is the gold standard for hepatic parenchymal evaluation, this is not feasible in such a large population of patients or as a way of monitoring change over time. This review discusses MRI-based techniques for assessing hepatic fibrosis, hepatic steatosis, and hepatic iron content, with discussions of both current techniques and future advancements.

Germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) at diagnosis is associated with superior long-term outcomes compared to non-GCB-DLBCL in patients treated with conventional chemo-immunotherapy. Whether cell of origin (COO) by Hans algorithm retains its prognostic significance in patients with (R/R) relapsed/refractory DLBCL undergoing autologous hematopoietic cell transplant (auto-HCT) is not well established. Three hundred and fifty-seven patients underwent auto-HCT between 2005 and 2018. The COO status was determined in 284 patients and these were included in the analysis. One hundred ninety-four patients had GCB-DLBCL while 90 had non-GCB-DLBCL. Median follow up was 1.7 (0-13) years. The GCB-DLBCL was associated with inferior 5-year overall survival at 44% (95%CI, 36-52) versus 64% (95%CI, 54-77) (P = .004) and a higher relapse incidence at 67% (95%CI, 58-74) versus 49% (95%CI, 35-60) (P = .01) in the non-GCB-DLBCL. The difference between GCB and non-GCB-DLBCL remained statistically significant in multivariate analysis. Additionally, response at the time of transplant was an independent prognostic factor. GCB-DLBCL was enriched in double-hit and triple hit phenotype based on available fluorescence in situ hybridization data. These results suggest an enrichment of high-risk genetic rearrangements in R/R GCB-DLBCL resulting in limited efficacy of auto-HCT.

Introduction Chemotherapy prolongs the survival of patients with advanced and metastatic tumors. Since the liver plays an active role in the metabolism of chemotherapy agents, hepatic injury is a common adverse effect. The purpose of this study is to compare a novel quantitative chemical shift encoded magnetic resonance imaging (CSE-MRI) method with conventional T1-weighted In and Out of phase (T1 IOP) MR for evaluating the reproducibility of the methods in an oncologic population exposed to chemotherapy. Materials and methods This retrospective study was approved by the institutional review board with a waiver for informed consent. The study included patients who underwent chemotherapy, no suspected liver iron overload, and underwent upper abdomen MRI. Two radiologists independently draw circular ROIsin the liver parenchyma. The fat fraction was calculated from IOP imaging and measured from IDEAL-IQ fat fraction maps. Two different equations were used to estimate fat with IOP sequences. Intra-class correlation coefficient and repeatability coefficient were estimated to evaluate agreement between two readers on iron level and fat fraction measurement. Results CSE-MRI showed a higher reliability in fat quantification compared with both IOP methods, with a substantially higher inter-reader agreement (0.961 vs 0.372). This has important clinical implications. Conclusion The novel CSE-MRI method described here provides increased reproducibility and confidence in diagnosing hepatic steatosis in a oncologic clinical setting. IDEAL-IQ has been proved to be more reproducible than conventional IOP imaging.

Obtaining a specific diagnosis in the nontraumatic acute abdomen can be clinically challenging, because a wide range of disease processes affecting a number of different organ systems may have very similar presentations. Although computed tomography and ultrasound examination are the imaging tests most commonly used to evaluate the acute abdomen, MRI can often offer comparable diagnostic performance, and may be considered when other modalities are equivocal, suboptimal, or contraindicated. In some circumstances, MRI is emerging as an appropriate first-line imaging test.

Context Waldenstrom macroglobulinemia (WM) is a rare lymphoma for which scant comparative data exist to guide frontline therapy. Objective To compare the efficacy of the most frequently used rituximab-based fixed-duration anti-WM regimens in routine practice [rituximab, bendamustine (R-Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR)] to inform clinicians about the benefits/limitations of choosing one regimen over the other. Design A retrospective cohort study. Participants Patients with active WM seen at Mayo Clinic Rochester, Arizona, and Florida campuses between 10/01/2000 and 10/31/2019 who received R-Benda, DRC, or BDR as primary therapy were included. Outcomes Measures Overall response rate (ORR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), time-to-next therapy (TTNT) and treatment related adverse-effects (AEs) based on the three treatment regimens. The MYD88L265P mutation status was assessed using allele-specific polymerase-chain-reaction (sensitivity 1%). Response rates were assessed by Consensus Criteria. Time-to-event analyses were performed from the frontline therapy, using Kaplan-Meier method. CTCAE v4.03 was used to grade toxicities. Results The study included 220 patients with active WM who were treated with R-Benda (n=83), DRC (n=92) or BDR (n=45). The median follow-up was 4.5 (95% CI: 4-5) years. The R-Benda cohort demonstrated superior ORR (98%), in comparison to DRC (78%) or BDR (84%) cohorts, p=0.003. Similarly, longer PFS was evident with R-Benda use [median 5.2 versus 4.3 (DRC) and 1.8 years (BDR), p=0.0003]. The TTNT favored R-Benda [median, not-reached, versus 4.4 (DRC) and 2.6 years (BDR), p=0.0002]. These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p=0.77. In a subset analysis of 142 patients genotyped for MYD88L265P mutation, the ORR, PFS and TTNT were unaffected by the MYD88 signature within each cohort. Toxicity profiles across the three groups were comparable, barring a higher incidence of neutropenia and neuropathy in patients who received R-Benda and BDR regimens, respectively. Conclusions The ORR, PFS and TTNT with R-Benda are superior compared to DRC or BDR in treatment-naive patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88L265P mutation status.

Myelofibrosis is a myeloproliferative neoplasm that is characterized by splenomegaly, profound symptom burden, and cytopenias. JAK inhibitor therapy offers improvements in splenomegaly, symptom burden, and potentially survival; however, cytopenias remain a significant challenge. Danazol has previously demonstrated improvements in myelofibrosis-associated anemia. We conducted a phase II clinical trial evaluating the efficacy and tolerability of combination therapy with ruxolitinib, an oral JAK inhibitor, and danazol. Fourteen intermediate or high-risk MF patients were enrolled at 2 institutions. Responses per IWG-MRT criteria were stable disease in 9 patients (64.2%) clinical improvement in 3 (21.4%) all of which were spleen responses, partial response in 1 (7.1%) and progressive disease in 1 (7.1%). Despite limited IWG-MRT response, stabilization of anemia and thrombocytopenia was demonstrated. In JAK inhibitor naïve patients, 4/5 (80%) had stable or increasing hemoglobin. Of the 9 patients on prior JAK inhibitor, 5 patients (55.5%) and 8 patients (88.9%) had stable or increasing hemoglobin or platelet levels, respectively. Adverse events possibly related included grade 3 or greater hematologic toxicity in ten patients (71.4%) and non-hematologic toxicity in two patients (14.3%). Although combination therapy did not lead to increased hematologic response per IWG-MRT criteria, hematologic stabilization was observed and may be clinically useful.

Purpose The detection of small parenchymal hepatic lesions identified by preoperative imaging remains a challenge for traditional pathologic methods in large specimens. We developed a magnetic resonance imaging (MRI) compatible localization device for imaging of surgical specimens aimed to improve identification and localization of hepatic lesions ex vivo. Materials and methods The device consists of two stationary and one removable MR-visible grids lined with silicone gel, creating an orthogonal 3D matrix for lesion localization. To test the device, five specimens of swine liver with a random number of lesions created by microwave ablation were imaged on a 3 T MR scanner. Two readers independently evaluated lesion coordinates and size, which were then correlated with sectioning guided by MR imaging. Results All lesions ( n = 38) were detected at/very close to the expected localization. Inter-reader agreement of lesion localization was almost perfect (0.92). The lesion size estimated by MRI matched macroscopic lesion size in cut specimen (± 2 mm) in 34 and 35, respectively, out of 38 lesions. Conclusion Use of this MR compatible device for ex vivo imaging proved feasible for detection and three-dimensional localization of liver lesions, and has potential to play an important role in the ex vivo examination of surgical specimens in which pathologic correlation is clinically important.

Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy. A group of physicians at Mayo Clinic with expertise in the care of patients with multiple myeloma regularly evaluates the evolving literature on the biology and therapy for multiple myeloma and issues guidelines on the optimal care of patients with this disease. In this article, the latest recommendations on the diagnostic evaluation of relapsed multiple myeloma and decision trees on how to treat patients at various stages of their relapse (off study) are provided together with the evidence to support them.

To quantify the trends in imaging use for the diagnosis of appendicitis.A retrospective study covering a 22-year period was conducted at an academic medical center. Patients were identified by International Classification of Diseases-9 diagnosis code for appendicitis. Medical record data extraction of these patients included imaging test used (ultrasound, CT, or MRI), gender, age, and body mass index (BMI). The proportion of patients undergoing each scan was calculated by year. Regression analysis was performed to determine whether age, gender, or BMI affected imaging choice.The study included a total of 2,108 patients, including 967 (43.5%) females and 599 (27%) children (18 years old). CT use increased over time for the entire cohort (2.9% to 82.4%, P.0001), and each subgroup (males, females, adults, children; P.0001 for each). CT use increased more in females and adults than in males and children, but differences in trends were not statistically significant (male versus female, P = .8; adult versus child, P = .1). The percentage of patients who had no imaging used for the diagnosis of appendicitis decreased over time (P.0001 overall and for each subgroup), and no difference was found in trends between complementary subgroups (male versus female, P = .53; adult versus child, P = .66). No statistically significant changes were found in use of ultrasound or MRI over the study period. With increasing BMI, CT was more frequently used.Of those diagnosed with appendicitis at an academic medical center, CT use increased more than 20-fold. However, no statistically significant trend was found for increased use of ultrasound or MRI.

Background Waldenstrom macroglobulinemia (WM) is a rare and incurable lymphoproliferative disease. The advent of novel therapies such as proteasome inhibitors and monoclonal antibodies has expanded the therapeutic armamentarium for treatment of WM. Due to the rare nature of the disease, most reported studies on the use of autologous stem cell transplant (ASCT) in WM are small and retrospective in nature. Since the advent of novel agents, few studies have reported whether these agents influence the disease course in the ASCT setting. Herein we present outcomes of patients with WM who underwent ASCT at three Mayo Clinic sites. Methods Records of all patients with WM who underwent ASCT between 8/2005 and 11/2017 were reviewed. Time-to-event analyses were performed from ASCT using the Kaplan-Meier method. Response criteria from the 6th International WM Workshop were used. Results Patient characteristics are described in Table 1. Two patients had large cell transformation; one prior to ASCT and one post-ASCT. The overall response rate to transplant was 100% (3 complete responses [CR], 8 very good partial responses [VGPR] and 6 partial responses [PR]). After a median follow-up of 58 months, the median progression free survival (PFS) after ASCT was 66 months and the median overall survival (OS) was not reached (NR). The relapse rate was 65% (11 out of 17 patients relapsed). The treatment related mortality was 0% and relapse mortality was 12%. The 2 deaths in the cohort were the patients who had large cell transformation and they died at 18 and 25 m post-ASCT, respectively. The treatment immediately prior to transplant, irrespective of the use of rituximab (R), did not impact the PFS (median PFS 47 m with prior R v 66 m without prior R, p=0.82, Fig. 1A). Similarly, prior exposure to a bortezomib (V)-based regimen did not impact the PFS (median NR v. 47 m, p=0.19 respectively, Fig. 1B). Achieving ≥VGPR after ASCT did not result in superior PFS compared to patients who achieved a PR (47 m vs. NR, p=0.59, respectively, Fig. 1C). Patients who had ASCT after >2 lines of therapy had an inferior PFS compared to patients who had ASCT ≤2 lines of therapy (41 m vs. 112 m, p=0.03, respectively, Fig 1D). Patients with large cell transformation at any point, had inferior PFS after transplant compared to those who did not (10m vs. 66m, p Conclusions ASCT for patients with WM is a safe and efficacious treatment modality with an ORR of 100% and affords eligible patients a median treatment-free interval of 4 years. The use of V or R prior to ASCT does not impact the depth of response or PFS after ASCT. To obtain the maximum PFS benefit, ASCT should be performed earlier in the disease course, prior to receiving more than 2 lines of therapy.

Highlights • Hemophilic pseudotumor is a rare complication of Hemophilia A and B. • Diagnosis requires a high index of suspicion-especially in non-hemophilic patients. • Radiographic findings are similar to that of malignant tumors. • Surgical intervention remains the mainstay of treatment. • Pre-operative embolization has been shown to reduce intra-operative bleeding., Introduction Hemophilic pseudotumor is a rare but well documented complication seen in approximately 1–2% of patients with hemophilia. The incidence continues to decrease, likely because of increasingly sophisticated techniques in managing factor deficiency. We present a case of hemophilic pseudotumor in a patient without hemophilia, an exceptionally rare entity, and outline a hybrid approach to treatment. Presentation of case The patient presented with a left sided iliopsoas mass and associated radiculopathy, with a history of a poorly characterized bleeding diathesis and Noonan’s syndrome. He had no history of trauma and was not being treated with anti-coagulation. Of note, factors VIII, IX and XI were normal. An open biopsy was consistent with hemophilic pseudotumor. The patient underwent a hybrid procedure of preoperative embolization of the left internal iliac and left deep circumflex arteries followed by surgical debridement and resection, with an excellent outcome. Discussion Hemophilic pseudotumor is rarely seen in patients with hemophilia, and even less frequently in patients without. Trauma is often the inciting event. A high index of clinical suspicion is required in order to secure the diagnosis, as the radiographic appearance is non-specific. Our patient had no history of trauma, although we question whether his underlying bleeding diathesis may have predisposed him to developing the pseudotumor. Surgery remains the cornerstone of management in these cases. Conclusion Within the literature, there are only two other cases of hemophilic pseudotumor occurring in a non-hemophiliac patient, highlighting the rarity of this case and the associated diagnostic dilemma.

Recent literature suggests that the layer of adipocytes embedded in the skin below the dermis is far from being an inert spacer material. Instead, this layer of dermal white adipose tissue (dWAT) is a regulated lipid layer that comprises a crucial environmental defense. Among all the classes of biological molecules, lipids have the lowest thermal conductance and highest insulation potential. This property can be exploited by mammals to reduce heat loss, suppress brown adipose tissue activation, reduce the activation of thermogenic programs, and increase metabolic efficiency. Furthermore, this layer responds to bacterial challenge to provide a physical barrier and antimicrobial disinfection, and its expansion supports the growth of hair follicles and regenerating skin. In sum, this dWAT layer is a key defensive player with remarkable potential for modifying systemic metabolism, immune function, and physiology. In this review, we discuss the key literature illustrating the properties of this recently recognized adipose depot.

Immunoglobulin light chain amyloidosis (AL amyloidosis) has an incidence of approximately 1 case per 100,000 person-years in Western countries. The rarity of the condition not only poses a challenge for making a prompt diagnosis but also makes evidenced decision making about treatment even more challenging. Physicians caring for patients with AL amyloidosis have been borrowing and customizing the therapies used for patients with multiple myeloma with varying degrees of success. One of the biggest failings in the science of the treatment of AL amyloidosis is the paucity of prospective trials, especially phase 3 trials. Herein, we present an extensive review of the literature with an aim of making recommendations in the context of the best evidence and expert opinion.

Background Determination of high risk via genetics plays a significant role in prognosis of disease outcomes in MM. More recently, MRD is emerging as an important prognostic marker and will potentially be used as a surrogate marker in clinical trials. So far, there is limited data on the association between cytogenetics in MM and MRD status. We conducted this study with the hypothesis that cytogenetics in MM would be predictive of MRD status after treatment with high dose chemotherapy and SCT. Methods Patients who underwent SCT for MM and had MRD data available (tested at day +100 post SCT) were included in the study. Clinical data was obtained via retrospective chart review. Cytogenetic risk (CyR) were classified into high [-17p, t(4;14), t(14;16), 1q gain, t(14;20)] and standard risk [all others including trisomies, t(11;14), t(6;14)], based on the updated mSMART criteria. Disease and SCT related characteristics were compared by MRD status. Comparisons were performed using the chi-squared test for categorical variables and Wilcoxon rank sum test for continuous variables. Results A total 144 patients were identified. Median age at diagnosis was 60 years (range, 37-76 years) and at SCT was 62 years (range, 38–78 years). Eighty-eight (61%) were men. CyR was standard risk in 103 (72%) and high risk in 41 (28%) patients. Flow cytometry (FC) was used in 78 (54%) patients while next generation sequencing (NGS) (Clonoseq, Adaptive Biotechnology) in 66 (46%) for MRD detection. In the 66 patients who had both test results available, NGS report was used for this analysis. Amongst these patients, MRD results were discordant in 37 out of 66 (56%) patients (i.e. FC was negative but NGS was positive). This is expected due to difference in sensitivities of the two methods (i.e. 10−4 to 2 × 10−5 for FC and 10−6 for NGS). In the comparison of patients who had high risk vs standard risk cytogenetics, rates of MRD negativity were not statistically significantly different (MRD negative in high risk 37% vs standard risk 32%, p = 0.6) (Figure 1). Several other disease and SCT related characteristics were examined for association with MRD negativity (M-spike levels, presence of extramedullary disease at diagnosis, type of light chain/ heavy chain involvement with MM, prior treatments, use of novel agents, number of lines of induction prior to SCT, disease response at SCT, cell dose and conditioning regimen). Of these, response at SCT was the only variable that was statistically significantly associated with MRD negative results in univariate analysis (Figure 1). Conclusions In our study, no association was seen between cytogenetic risk at baseline to achievement of MRD negative status post SCT. This is unexpected and possibly related to the small sample size. This clinical question, however, remains to be of significant clinical utility and should be explored in a larger database.

Although reduced-intensity conditioning has become standard of care for patients with hematologic malignancies undergoing allogeneic hematopoietic cell transplantation (HCT), the optimum regimen has yet to be defined, and may depend on pretransplantation patient– and/or disease-specific risk factors. We report here results in 100 adults, ages 18 to 69, with high-risk hematologic malignancy who received conditioning with fludarabine, carmustine, melphalan, and rabbit antithymocyte globulin (FBM-A). Outcomes were stratified using the disease risk index (DRI) as published by Armand et al. (Blood 2012;120:905-913). Median age was 56, and patients were ineligible for standard myeloablative conditioning because of age, organ dysfunction, or prior autologous HCT. Patients underwent transplantation for myeloid (acute myelogenous leukemia, n = 40; myelodysplastic syndrome, n = 24; myelofibrosis, n = 13; other myeloid, n = 2) or lymphoid (acute lymphoblastic leukemia, n = 8; non-Hodgkin lymphoma, n = 8; Hodgkin lymphoma, n = 4, chronic lymphocytic leukemia, n = 1) malignancy. Donors were related in 26 patients (22 matched, 4 mismatched at 1 antigen) and unrelated in 74 (mismatched at 1 or 2 HLA loci in 33); grafts were peripheral blood stem cells in 97 patients, bone marrow in 2, and double cord in 1. According to the DRI, 68 patients were classified as low (n = 1) or intermediate risk (n = 67), and 32 were classified as high (n = 28) or very high risk (n = 4). With a median follow-up of surviving patients of 18 months, the Kaplan-Meier estimate of overall survival at 2 years for patients in the low/intermediate risk group is 80%, compared with 66% in the high/very high group (P = .11). Two-year cumulative incidence of relapse and nonrelapse mortality in the low/intermediate group are 9.9% and 15%, versus 25% and 19% in the high/very high group (respective P values .07 and .81). The cumulative incidence of acute graft-versus-host (GVHD) grades III to IV at 100 days was 8.1%, and the incidence of National Institutes of Health–defined moderate to severe chronic GVHD was 22% at 2 years. No deaths were attributable to chronic GVHD. Survival was not influenced by age, hematopoietic comorbidity index score, donor type, donor gender, or presence of mismatch. We conclude that FBM-A is an effective and safe conditioning regimen for adults up to age 69 with hematologic malignancies who have low-, intermediate-, or high-risk scores according to the DRI.

Background Intraosseous access has been used increasingly with proven efficacy in emergent situations for adults when intravenous access could not be obtained. Objective Our aim was to demonstrate if tibial intraosseous (IO) is an effective route for iodinated contrast administration and pulmonary vasculature visualization. Case Report We report on an obtunded patient requiring a computed tomography angiogram to help with diagnosis and tibial IO was the only viable access appropriate to withstand the pressure of a computed tomography iodinated contrast load. Tibial IO access was used successfully for administration of iodinated contrast to evaluate for massive pulmonary embolism in an obtunded patient in extremis secondary to cardiovascular instability. Conclusions The pulmonary arteries were opacified and demonstrated a high-quality CT angiogram can be done via tibial IO device.

The prognosis for patients with Philadelphia-negative myeloproliferative neoplasms (MPN) who evolve into acute myeloid leukemia (AML) or blast phase (MPN-BP) is extremely poor. Although allogeneic stem cell transplantation (allo-SCT) is considered potentially curative, very few patients have been reported who have undergone allo-SCT for MPN-BP; therefore the success rate remains unknown. In a retrospective review, we identified 13 patients with an MPN transformation to blast phase after a median 9 years (range 5 months to 30 years); 8 (median age 55) continued to allo-SCT within 6 months. Induction chemotherapy cleared blood/marrow blasts in 60% (6/10) (2 declined therapy, 1 had early death). At the time of allo-SCT, 5/8 patients were in complete remission (CR) of their leukemia or had returned to MPN chronic phase (CP), 2 had residual blood blasts and 1 was refractory with >5% marrow blasts. At follow-up (median 20.3 months), 6 patients are alive in CR of both their leukemia/MPN. All 5 patients in CR/CP at pre-allo-SCT remain alive in remission, while 2/3 with persistent blood/marrow blasts relapsed and expired. We conclude that MPN-BP can be cured by allo-SCT in a significant percentage of patients, but that adequate leukemic clearance prior to allo-SCT offers an optimal outcome.

Hamstring strain injuries often occur near the proximal musculotendon junction (MTJ) of the biceps femoris. Post-injury remodeling can involve scar tissue formation, which may alter contraction mechanics and influence re-injury risk. The purpose of this study was to assess the affect of prior hamstring strain injury on muscle tissue displacements and strains during active lengthening contractions. Eleven healthy and eight subjects with prior biceps femoris injuries were tested. All previously injured subjects had since returned to sport and exhibited evidence of residual scarring along the proximal aponeurosis. Subjects performed cyclic knee flexion-extension on an MRI-compatible device using elastic and inertial loads, which induced active shortening and lengthening contractions, respectively. CINE phase-contrast imaging was used to measure tissue velocities within the biceps femoris during these tasks. Numerical integration of the velocity information was used to estimate two-dimensional tissue displacement and strain fields during muscle lengthening. The largest tissue motion was observed along the distal MTJ, with the active lengthening muscle exhibiting significantly greater and more homogeneous tissue displacements. First principal strains magnitudes were largest along the proximal MTJ for both loading conditions. The previously injured subjects exhibited less tissue motion and significantly greater strains near the proximal MTJ. We conclude that localized regions of high tissue strains during active lengthening contractions may predispose the proximal biceps femoris to injury. Furthermore, post-injury remodeling may alter the in-series stiffness seen by muscle tissue and contribute to the relatively larger localized tissue strains near the proximal MTJ, as was observed in this study.

Multiple myeloma is a malignant plasma cell neoplasm that affects more than 20,000 people each year and is the second most common hematologic malignancy. It is part of a spectrum of monoclonal plasma cell disorders, many of which do not require active therapy. During the past decade, considerable progress has been made in our understanding of the disease process and factors that influence outcome, along with development of new drugs that are highly effective in controlling the disease and prolonging survival without compromising quality of life. Identification of well-defined and reproducible prognostic factors and introduction of new therapies with unique modes of action and impact on disease outcome have for the first time opened up the opportunity to develop risk-adapted strategies for managing this disease. Although these risk-adapted strategies have not been prospectively validated, enough evidence can be gathered from existing randomized trials, subgroup analyses, and retrospective studies to develop a working framework. This set of recommendations represents such an effort—the development of a set of consensus guidelines by a group of experts to manage patients with newly diagnosed disease based on an interpretation of the best available evidence.

Objective The purpose of this study is to describe a new approach for addressing the intraoperative management of intercostal arteries during thoracoabdominal aortic aneurysm (TAAA) repair, using preoperative spinal MRA for detection of intercostal arteries supplying the anterior spinal artery. Methods Patients undergoing TAAA repair from August 2005 to September 2007 were included. Spinal artery MRA was performed to identify the anterior spinal artery, the artery of Adamkiewicz, and its major intercostal source artery (SA-AAK). Intraoperative spinal cord protection was carried out using standard techniques. Important intercostal arteries were either preserved or reimplanted as a button patch after removing aortic clamps. Demographic and perioperative data were collected for review. Analysis was performed with Fisher's exact test or Student's t- test, where applicable, using SAS ver. 8.0 (Cary, NC). Results Spinal artery MRA was performed in 27 patients. The SA-AAK was identified in 85% of preoperative studies. Open or endovascular repair was performed in 74% and 26% of patients, respectively. The SA-AAK was preserved or reimplanted in 13 (65%) of patients who underwent open repair. A mean of 1.67 (range 1–3) intercostal arteries were reimplanted. All patients undergoing endovascular repair necessitated coverage of the SA-AAK. No patient developed immediate or delayed paraplegia. Longer mean operative times in the reimplanted cohort were not statistically significant (330 versus 245 min, P = 0.1). Conclusion The SA-AAK identified by MRA can be preserved or safely reimplanted after TAAA repair. Further study is warranted to determine if selective intercostal reimplantation can reduce the risk of immediate or delayed paraplegia.

The statistical properties of background noise such as its standard deviation and mean value are frequently used to estimate the original noise level of the acquired data. This requires the knowledge of the statistical intensity distribution of the background signal, that is, the probability density of the occurrence of a certain signal intensity. The influence of many new MRI techniques and, in particular, of various parallel-imaging methods on the noise statistics has neither been rigorously investigated nor experimentally demonstrated yet. In this study, the statistical distribution of background noise was analyzed for MR acquisitions with a single-channel and a 32-channel coil, with sum-of-squares (SoS) and spatial-matched-filter (SMF) data combination, with and without parallel imaging using k-space and image-domain algorithms, with real-part and conventional magnitude reconstruction and with several reconstruction filters. Depending on the imaging technique, the background noise could be described by a Rayleigh distribution, a noncentral chi-distribution or the positive half of a Gaussian distribution. In particular, the noise characteristics of SoS-reconstructed multichannel acquisitions (with k-space-based parallel imaging or without parallel imaging) differ substantially from those with image-domain parallel imaging or SMF combination. These effects must be taken into account if mean values or standard deviations of background noise are employed for data analysis such as determination of local noise levels. Assuming a Rayleigh distribution as in conventional MR images or a noncentral chi-distribution for all multichannel acquisitions is invalid in general and may lead to erroneous estimates of the signal-to-noise ratio or the contrast-to-noise ratio.

Rationale and Objectives Existing cardiac imaging methods do not allow for improved temporal resolution when considering a targeted region of interest (ROI). The imaging method presented here enables improved temporal resolution for ROI imaging (namely, a reconstruction volume smaller than the complete field of view). Clinically, temporally targeted reconstruction would not change the primary means of reconstructing and evaluating images, but rather would enable the adjunct technique of ROI imaging, with improved temporal resolution compared with standard reconstruction (∼20% smaller temporal scan window). In gated cardiac computed tomography (CT) scans improved temporal resolution directly translates into a reduction in motion artifacts for rapidly moving objects such as the coronary arteries. Materials and Methods Retrospectively electrocardiogram gated coronary angiography data from a 64-slice CT system were used. A motion phantom simulating the motion profile of a coronary artery was constructed and scanned. Additionally, an in vivo study was performed using a porcine model. Comparisons between the new reconstruction technique and the standard reconstruction are given for an ROI centered on the right coronary artery, and a pulmonary ROI. Results In both a well-controlled motion model and a porcine model results show a decrease in motion induced artifacts including motion blur and streak artifacts from contrast enhanced vessels within the targeted ROIs, as assessed through both qualitative and quantitative observations. Conclusion Temporally targeted reconstruction techniques demonstrate the potential to reduce motion artifacts in coronary CT. Further study is warranted to demonstrate the conditions under which this technique will offer direct clinical utility. Improvement in temporal resolution for gated cardiac scans has implications for improving: contrast enhanced CT angiography, calcium scoring, and assessment of the pulmonary anatomy.

Cardiac MRI has become a routinely used imaging modality in the diagnosis of cardiovascular disease and is considered the clinically accepted gold standard modality for the assessment of cardiac function and myocardial viability. In recent years, commercially available clinical scanners with a higher magnetic field strength (3.0 T) and dedicated multi-element coils have become available. The superior signal-to-noise ratio (SNR) of these systems has lead to their rapid acceptance in cranial and musculoskeletal MRI while the adoption of 3.0 T for cardiovascular imaging has been somewhat slower. This review article describes the benefits and pitfalls of magnetic resonance imaging of ischemic heart disease at higher field strengths. The fundamental changes in parameters such as SNR, transversal and longitudinal relaxation times, susceptibility artifacts, RF (B1) inhomogeneity, and specific absorption rate are discussed. We also review approaches to avoid compromised image quality such as banding artifacts and inconsistent or suboptimal flip angles. Imaging sequences for the assessment of cardiac function with CINE balanced SSFP imaging and MR tagging, myocardial perfusion, and delayed enhancement and their adjustments for higher field imaging are explained in detail along with several clinical examples. We also explore the use of parallel imaging at 3.0 T to improve cardiac imaging by trading the SNR gain for higher field strengths for acquisition speed with increased coverage or improved spatial and temporal resolution. This approach is particularly useful for dynamic applications that are usually limited to the duration of a single breath-hold.

Multiple myeloma is a neoplastic plasma cell dyscrasia that on a yearly basis affects nearly 17,000 individuals and kills more than 11,000. Although no cure exists, many effective treatments are available that prolong survival and improve the quality of life of patients with this disease. The purpose of this consensus is to offer a simplified, evidence-based algorithm of decision making for patients with newly diagnosed myeloma. In cases in which evidence is lacking, our team of 18 Mayo Clinic myeloma experts reached a consensus on what therapy could generally be recommended. The focal point of our strategy revolves around risk stratification. Although a multitude of risk factors have been identified throughout the years, including age, tumor burden, renal function, lactate dehydrogenase, beta2-microglobulin, and serum albumin, our group has now recognized and endorsed a genetic stratification and patient functional status for treatment.

Bisphosphonates are effective in the prevention and treatment of bone disease in multiple myeloma (MM). Osteonecrosis of the jaw is Increasingly recognized as a serious complication of long-term bisphosphonate therapy. Issues such as the choice of bisphosphonate and duration of therapy have become the subject of intense debate given patient safety concerns. We reviewed available data concerning the use of bisphosphonates in MM. Guidelines for the use of bisphosphonates in MM were developed by a multidisciplinary panel consisting of hematologists, dental specialists, and nurses specializing in the treatment of MM. We conclude that intravenous pamidronate and intravenous zoledronic acid are equally effective and superior to placebo in reducing skeletal complications. Pamidronate is favored over zoledronic acid until more data are available on the risk of complications (osteonecrosis of the jaw). We recommend discontinuing bisphosphonates after 2 years of therapy for patients who achieve complete response and/or plateau phase. For patients whose disease is active, who have not achieved a response, or who have threatening bone disease beyond 2 years, therapy can be decreased to every 3 months. These guidelines were developed in the Interest of patient safety and will be reexamined as new data emerge regarding risks and benefits.

* Corresponding author. E-mail address: gold@stanford.edu (G.E. Gold). Osteoarthritis is an important cause of disability in our society, affecting millions and resulting in loss of time at work and activity limitations [1– 5]. Osteoarthritis is primarily a disease of articular cartilage from injury or degeneration [6–8]. Many treatment strategies for cartilage damage have been proposed [9–11], but methods for assessment of the effectiveness of these therapies are limited to clinical evaluation and occasional opportunities for arthroscopic examination. MR imaging offers a noninvasive means of assessing the degree of damage to cartilage and adjacent bone, and effectiveness of treatment. The accepted gold standard for monitoring cartilage damage in the shoulder is arthroscopy, with high resolution and the ability to probe the cartilage surface. Arthroscopy is invasive and expensive, and allows only visual inspection of the cartilage surface for such abnormalities as color changes and fissuring. Arthroscopy also allows probing of cartilage, which involves using a small metallic probe to apply pressure on the cartilage surface to assess softening (chondromalacia). Many imaging methods are available to assess articular cartilage in the shoulder. Conventional radiography can be used to detect gross loss of cartilage, evident as narrowing of the glenohumeral distance [12], but it does not image cartilage directly. Secondary changes, such as osteophyte formation or subchondral cysts, can be seen, but conventional radiography is insensitive to early chondral damage. Arthrography, alone or com

Neurogenic tumors can arise from neural cells in any location; however, they commonly are found in the mediastinum and, more specifically, most often are located in the posterior compartment. Neurogenic tumors can be benign or malignant, with a wide array of both clinical and pathologic features that are commonly classified by the cell type of origin. These tumors are usually detected on routine chest radiograph, and a computed tomographic scan is required to obtain more information about involvement of local structures. A magnetic resonance imaging scan may be necessary if a dumbbell-shaped component is identified or suspected. Treatment options vary depending on the presentation, but most often surgical resection is recommended. Whereas patients with benign neurogenic tumors have an excellent prognosis with complete surgical resection, patients with malignant neurogenic tumors still have poor long-term survival prospects.

A study was made of obstetrical care before and after consolidation of obstetrical services in Saskatoon. The effect of service amalgamation upon the degree of intervention in labours managed by family doctors was determined by examining Caesarean section rates and intrapartum risk score changes. This study suggests that there has been no change in the intervention rates in family doctor-managed labours in Saskatoon as a result of amalgamation of obstetrical services in that city.

Background. We questioned whether results of myotomy for achalasia are influenced by previous pneumatic dilation and whether surgical outcome is influenced by a dilation-related perforation necessitating urgent operation. Methods. We performed a retrospective analysis of 60 patients who underwent transthoracic myotomy and fundoplication from 1977 to 1995. Dysphagia, heartburn, pain, and regurgitation were scored on a scale of 0 to 3 and results were classified according to combined symptom score. Results. Dilation was performed before myotomy once in 15 patients, twice in 25, 3 times or more in 9, and never in 11 patients. Operation was urgent due to perforation in 6 patients (10%). There was no postoperative leak or mortality. Overall symptom score at last follow-up (57 ± 8 months; 90% of patients) was improved compared with preoperative score (2.1 ± 0.3 months versus 5.1 ± 0.2 months; p Conclusions. Myotomy and partial fundoplication is an effective technique for management of achalasia. Results are unaffected by the need for urgent operation for perforation and are unrelated to whether pneumatic dilation is performed preoperatively.

Objectives: It is not known whether a normal diffusing capacity for carbon monoxide permits safe lung resection in patients with marginal spirometric values, or whether normal spirometric values negate the adverse effects of a low diffusing capacity. The purposes of this study were (1) to determine the best predictors of morbidity and mortality and (2) to assess whether interactions exist between diffusing capacity and spirometry that help estimate outcome after major lung resection. Design: A retrospective analysis of 376 patients who underwent lung resection was performed. Three hundred three had lung cancer and 73 had other disease. Two hundred eighty-four underwent lobectomy/bilobectomy and 92 had pneumonectomy. We assessed the relationship of 23 preoperative variables to 18 postoperative events classified into categories as pulmonary or cardiac complications, overall morbidity, and operative mortality. Results:The best single predictor of complications was the percent predicted postoperative diffusing capacity. The incidences of pulmonary and cardiac complications, morbidity, and mortality were inversely related to predicted postoperative diffusing capacity percent (p < 0.004 for each). Multivariate logistic regression analyses identified only predicted postoperative diffusing capacity percent and age as significant independent predictors of pulmonary complications, morbidity, and death, and these with prior myocardial infarction predicted cardiac complications. There were no interactions between percent predicted postoperative forced expiratory volume in 1 second and predicted postoperative diffusing capacity percent in estimating risks of complications. Conclusion: Predicted postoperative diffusing capacity percent is the strongest single predictor of risk of complications and mortality after lung resection. There is little interrelationship of predicted postoperative diffusing capacity percent and predicted postoperative forced expiratory volume in 1 second, indicating that these values should be assessed independently in estimating operative risk. (J THORAC CARDIOVASC SURG 1995;109:275-83)

Background Prior reviews of esophageal perforation with delayed recognition have reported mortality rates as high as 66%. We performed a retrospective review of patients with nonmalignant esophageal perforation to assess the outcome of current management techniques. Patients and methods Charts were reviewed of all patients who were treated for nonmalignant esophageal perforation between 1980 and 1993. They were 23 men and 10 women, mean age 49 ± 3 years, 19 of whom were diagnosed early (≤24 hours) and 14 of whom were diagnosed late (>24 hours). Results Perforations were due to instrumentation (16), operative injury (7), spontaneous rupture (4), trauma (4), and other causes (2). Preexisting esophageal disease was identified in 23 patients (70%), including achalasia (9), stricture (7), varices (5), and other (2). Treatment included closure and fundoplication or muscle wrap (10), closure with or without pleural flap (7), resection only (7), resection and reconstruction (3), drainage only (4), and observation (2). Nonfatal complications included empyema (4), arrhythmia (3), persistent leak following attempted closure (2), and other (5). They occurred in 50% of both the early and late diagnosis groups and were of comparable severity in both. The overall mortality was 9% (3/33). Causes of death were sepsis (1) and multisystem organ failure (2). Mortality was 5% (1/19) in patients diagnosed early and 14% (2/14) of those diagnosed late. Conclusions Current mortality rates in nonmalignant esophageal perforation are improved compared to previously published rates of 19% for all patients with the condition, 9% following early and 29% following late diagnosis (47 patients overall). We conclude that, despite a high incidence of associated complications, the survival rate following nonmalignant esophageal perforation is improving and the impact of delayed recognition is decreasing.

Multiple Myeloma and Mantle Cell Lymphoma are well defined hematological malignancies. Understanding of their pathogeneses has led to new therapies and increased survival. We report on a 64-yr-old female who was diagnosed with mantle cell lymphoma in 2003, then multiple myeloma in 2010. We identified only few other cases of concomitant MM and MCL. We also explored the importance of t(11;14)(q13;q32). The development of these two disorders in the same patient may simply be due to chance; however, it may also represent a common genetic hit affecting the B-cell population leading to development of two different malignancies.

secreting tumors of the adrenal gland and ovary, McCune Albright syndrome, VanWyk-Grumbach syndrome, adrenal gland enzyme deficiencies and exogenous exposure to sex hormones. Sex hormone secreting tumors of the ovary are a rare cause of PPP. Although, it is well known that males can have human chorionic gonadotropin (hcg) secreting germ cell tumors which activate the LH receptors on the testicular Leydig cells resulting in testosterone secretion, the exact mechanism for a germ cell tumor to cause PPP in females is not known. There are case reports of females with mixed GCT/ stromal cell tumors of the ovary presenting with PPP but few describing a solitary GCT. In this case the pathology specimen did not find any component of sex cord tumor nor were the tumor markers associated with sex cord tumors elevated significantly. Based on this case report, it is important to consider GCTs in the differential diagnosis of PPP.