68Ga-PSMA PET/CT in Recurrent Prostate Cancer after Radical Prostatectomy Using PSMA-RADS Version 2.0.

BACKGROUND: 68Ga-PSMA PET/CT is superior to standard-of-care imaging for detecting regional and distant metastatic recurrent prostate cancer. The objective of our study was to evaluate the performance of 68Ga-PSMAPET/CT in our patient population, using the new PSMA-RADS version 2.0. METHODS: A total of 128 patients scanned with 68Ga-PSMA PET/CT for detection of recurrence after RP were analyzed with PSMA-RADS version 2.0. For the analysis of the detection rate, categories PSMA-RADS 3 to 5 were considered as "positive for malignancy" and 1-2 as "negative". RESULTS: According to PSMA-RADS v2.0, we classified patients as follows: 23 patients without PSMA-RADS because they were negative; PSMA-RADS 1: 10 patients; PSMA-RADS 2: 4 patients; PSMA-RADS 3A: 11 patients; PSMA-RADS 3B: 2 patients; PSMA-RADS 3C: 2 patients; PSMA-RADS 3D: 2 patients; PSMA-RADS 4: 13 patients; PSMA-RADS 5: 61 patients. CONCLUSIONS: The overall detection rate of 68Ga-PSMA PET/CT was 71%. By dividing the patients into fourgroups according to PSA level before examination, we obtained the following detection rates: PSA < 0.2 ng/mL 38%; 0.2 ≤ PSA < 0.5 ng/mL 57%; 0.5 ≤ PSA ≤ 1 ng/mL 77%; and PSA > 1 ng/mL 95%. CONCLUSION: Using PSMA-RADS version 2.0, we obtained detection rate values comparable with recent literature both in absolute terms and in relation to different PSA levels.

Imaging of primary retroperitoneal neoplasms.

Retroperitoneal soft tissue tumors are frequently incidental findings on imaging tests as Computed tomography (CT) or Magnetic Resonance Imaging (MRI). Retroperitoneal soft tissue tumors are rare and therefore not common in daily radiological practice. Clinician and radiologist'skills to set retroperitoneal soft tissue tumors at presentation is crucial for a correct patient management. So far, several diagnostic algorithms have been proposed to assess retroperitoneal masses, which have not been validated by case histories (2-5). The aim of this article is to evaluate a new classification of retroperitoneal masses using CT and MRI. KEY WORDS: CT, Diagnosis, MRI, Retroperitoneum, Soft tissue sarcoma.

Magnetic Resonance of Small Bowel Tumors.

Tumors of the small intestine represent less than 5% of all gastrointestinal tract neoplasms. Magnetic resonance (MR) imaging is rapidly increasing clinical acceptance to evaluate the small bowel and can be the initial imaging method to investigate small bowel diseases. MR examinations may provide the first opportunity to detect and characterize tumors of the small bowel. Intraluminal and extraluminal MR findings, combined with contrast enhancement and functional information, allow accurate diagnoses and consequently characterization of small bowel neoplasms. This article describes the MR findings of primary small bowel neoplasms and the MR findings for the differential diagnosis are discussed.

MR Enterography in paediatric patients with obscure gastrointestinal bleeding.

OBJECTIVES: To evaluate the performance of Magnetic Resonance enterography (MRE) in the diagnostic work-up of children presenting with obscure gastrointestinal bleeding (OGIB). MATERIALS AND METHODS: From January 2014 to January 2016, a single-centre prospective study was performed on all children between 0 and 16 years of age referred to the radiology department for OGIB. Each child underwent MRE examination after negative oesophagogastroduodenoscopy and ileocolonoscopy. MRE results were recorded. All patients proceeded to the related gold standard for diagnostic confirmation. RESULTS: 25 patients (mean age 10.8±4.5 years, range 4 months to 16 years) were included. MRE was diagnostic in 76% (19 of 25). The most frequent diagnoses were intestinal polyp (28%) and Meckel's diverticulum (16%). Sensitivity and specificity of MRE were 86% and 100% respectively. There were no reported complications during any of the examinations. CONCLUSION: MRE is a safe and accurate imaging modality in the evaluation of paediatric OGIB. Its diagnostic capability is comparable to current evidence for capsule endoscopy in this patient group. Further research with larger sample sizes and standardized control groups is warranted to improve our understanding of MRE in this application.

Current tecniques and new perpectives research of magnetic resonance enterography in pediatric Crohn's disease.

Crohn's disease affects more than 500000 individuals in the United States, and about 25% of cases are diagnosed during the pediatric period. Imaging of the bowel has undergone dramatic changes in the past two decades. The endoscopy with biopsy is generally considered the diagnostic reference standard, this combination can evaluates only the mucosa, not inflammation or fibrosis in the mucosa. Actually, the only modalities that can visualize submucosal tissues throughout the small bowel are the computed tomography (CT) enterography (CTE) with the magnetic resonance enterography (MRE). CT generally is highly utilized, but there is growing concern over ionizing radiation and cancer risk; it is a very important aspect to keep in consideration in pediatric patients. In contrast to CTE, MRE does not subject patients to ionizing radiation and can be used to detect detailed morphologic information and functional data of bowel disease, to monitor the effects of medical therapy more accurately, to detect residual active disease even in patients showing apparent clinical resolution and to guide treatment more accurately.

Diagnosis of Small-Bowel Diseases: Prospective Comparison of Multi-Detector Row CT Enterography with MR Enterography.

PURPOSE: To prospectively compare the accuracies of computed tomographic (CT) enterography and magnetic resonance (MR) enterography for the detection and characterization of small-bowel diseases. MATERIALS AND METHODS: The institutional review board approved the study protocol, and informed consent was obtained from all participants. From June 2009 to July 2013, 150 consecutive patients (81 men and 69 women; mean age, 38.8 years; range, 18-74 years), who were suspected of having a small-bowel disease on the basis of clinical findings and whose previous upper and lower gastrointestinal endoscopy findings were normal, underwent CT and MR enterography. Two independent readers reviewed CT and MR enterographic images for the presence of small-bowel diseases, for differentiating between inflammatory and noninflammatory diseases, and for extraenteric complications. The histopathologic findings of surgical (n = 23) and endoscopic (n = 32) biopsy specimens were used as the reference standard; the results of video-capsule endoscopy (n = 36) and clinical follow-up (n = 59) were used only to confirm the absence of small-bowel disease. RESULTS: MR and CT enterography were successfully performed in all 150 patients. Overall sensitivity, specificity, and accuracy, respectively, in identifying patients with small-bowel lesions were 75.9% (41 of 54), 94.8% (91 of 96), and 88.0% (132 of 150) for CT enterography and 92.6% (50 of 54), 99.0% (95 of 96), and 96.7% (145 of 150) for MR enterography. The sensitivity of MR enterography was significantly higher than that of CT enterography for the detection of both overall small-bowel diseases (P = .0159) and neoplastic diseases (P = .0412) but not for the detection of inflammatory diseases (P > .99) or noninflammatory and nonneoplastic diseases (P = .6171). CONCLUSION: MR enterography is more accurate than CT enterography in the detection of small-bowel diseases; MR enterography was more accurate in detecting neoplastic diseases in particular.

Stone disease in pregnancy: imaging-guided therapy.

Renal colic is the most frequent nonobstetric cause for abdominal pain and subsequent hospitalization during pregnancy. The physio-anatomical changes in the urinary tract and the presence of the fetus may complicate the clinical presentation and management of nephrolithiasis. Ultrasound (US) is the primary radiological investigation of choice. Magnetic resonance urography (MRU) and low-dose computed tomography (CT) have to be considered as a second- and third-line test, respectively. If a study that uses ionizing radiation has to be performed, the radiation dose to the fetus should be as low as possible. The initial management of symptomatic ureteric stones is conservative during pregnancy. Intervention will be necessary in patients who do not respond to conservative measures. Therefore, it is crucial to obtain a prompt and accurate diagnosis to optimize the management of these patients. Teaching Points • In pregnancy, renal colic is the most frequent nonobstetric cause for abdominal pain and hospitalization. • Magnetic resonance urography should be considered when ultrasound is nondiagnostic. • Low-dose CT should be considered as a last-line test during pregnancy.

Imaging for acute pelvic pain in pregnancy.

Acute pelvic pain in pregnancy presents diagnostic and therapeutic challenges. Standard imaging techniques need to be adapted to reduce harm to the foetus from X-rays because of their teratogenic and carcinogenic potential. Ultrasound remains the primary imaging investigation of the pregnant abdomen. Magnetic resonance imaging (MRI) has been shown to be useful in the diagnosis of gynaecological and obstetric problems during pregnancy and in the setting of acute abdomen during pregnancy. MRI overcomes some of the limitations of ultrasound, mainly the size of the gravid uterus. MRI poses theoretical risks to the foetus and care must be taken to minimise these with the avoidance of contrast agents. Teaching Points • Ultrasound and MRI are the preferred investigations for acute pelvic pain during pregnancy. • Ultrasound remains the primary imaging investigation because of availability and portability. • MRI helps differentiate causes of acute pelvic pain when ultrasound is inconclusive.

Noninflammatory conditions of the small bowel.

Magnetic resonance (MR) imaging has been playing an evolving role in evaluating noninflammatory small-bowel conditions, such as tumors and malabsorption syndrome. MR imaging has shown to be superior to other diagnostic methods in identifying tumors of the small bowel. MR enterography and MR enteroclysis are both valid for studying noninflammatory conditions of the small intestine, although MR enteroclysis may be considered the modality of choice because of its accuracy in the diagnosis of small-bowel neoplasms. Intraluminal and extraluminal MR findings, combined with contrast-agent enhancement and functional information, help to make an accurate diagnosis and consequently to characterize small-bowel diseases.

Magnetic resonance imaging of small bowel neoplasms.

Magnetic resonance (MR) imaging is rapidly increasing clinical acceptance to evaluate the small bowel and can be the initial imaging method to investigate small bowel diseases. MR examinations may provide the first opportunity to detect and characterize tumours of the small bowel. Intra- and extraluminal MR findings, combined with contrast enhancement and functional information, help to make an accurate diagnosis and consequently characterize small bowel neoplasms. MR enteroclysis should be recommended for the initial investigation in patients suspected of having small bowel tumours. In this article, the MR findings of primary small bowel neoplasms are described and the MR findings for the differential diagnosis are discussed.

Acute abdominal and pelvic pain in pregnancy: MR imaging as a valuable adjunct to ultrasound?

BACKGROUND: To investigate the usefulness of magnetic resonance imaging (MRI) in the evaluation of pregnant women with acute abdominal and pelvic pain after sonographically (US) indeterminate findings. METHODS: Forty pregnant patients with acute abdominal and/or pelvic pain, in whom ultrasound was indeterminate, were included in this study. Multiplanar MR images of the abdomen and pelvis were obtained and independently reviewed by two radiologists with discrepancies were resolved by consensus. RESULTS: Correlation of prospective clinical MR interpretations with surgical and obstetric records and clinical follow-up showed correct identification of disease entities in all 40/40 patients. The following disease processes were correctly identified using MRI in 21/40 patients: appendicitis (n = 5), ileal volvulus (n = 1), common bile duct lithiasis (n = 2), pubic chondrosarcoma (n = 1), uterine dehiscence (n = 1), placental hematoma (n = 3), iliac venous thrombosis (n = 2), ulcerative colitis (n = 1), acute pancreatitis (n = 1), hydronephrosis (n = 1), ovarian dermoid (n = 1), and ovarian torsion (n = 2). 19 of the 40 patients had normal findings on MR examinations and unremarkable follow-up. Interobserver agreement for lesion detection was excellent (0.95 k). CONCLUSION: Magnetic resonance imaging (MRI) is an accurate investigation in detecting the cause of acute abdominal and pelvic pain during pregnancy and should be considered after US indeterminate findings.

MR enterography versus capsule endoscopy in paediatric patients with suspected Crohn's disease.

OBJECTIVE: The aim of this prospective study was to compare the diagnostic yield of MR enterography (MRE) with small-bowel capsule endoscopy (SBCE) in paediatric patients with suspected Crohn's disease (CD). METHODS: Paediatric patients with suspected CD were considered eligible to be enrolled in the study. All patients underwent diagnostic work-up including 1.5-T MRE, ileo-colonoscopy and oesophagogastroduodenoscopy. SBCE was not performed if MRE showed SB stricture or extra-intestinal findings consistent with symptoms. RESULTS: Sixty consecutive paediatric patients (36 male; average age 14) were enrolled into the study. A positive diagnosis for CD was made in 19 patients, 29 had a negative result and 12 were affected by other gastro-intestinal conditions. SBCE was performed in 37 patients (61.7%); 23 patients were excluded (strictures in five, extra-intestinal findings in 11 and parents' refusal in seven cases). The accuracy, sensitivity, and specificity of MRE and SBCE were 98.3%, 100%, 97.6%, and 91.9%, 90.9%, 92.3%, respectively. CONCLUSION: Both MRE and SBCE are accurate methods for patients with suspected CD. MRE can be used as a primary imaging technique in suspected CD, in that it allows access to the ileal stricture, which forms a contra-indication for SBCE and provides extra-intestinal information.

Celiac disease: evaluation with dynamic contrast-enhanced MR imaging.

PURPOSE: To prospectively determine mural perfusion dynamics in patients with untreated celiac disease by using dynamic contrast material-enhanced magnetic resonance (MR) imaging and to compare these dynamics with those in a control population and in patients with celiac disease treated with a gluten-free diet. MATERIALS AND METHODS: Institutional review board approval and informed consent from all participants were obtained. Sixty consecutive patients with untreated celiac disease, 45 patients with celiac disease treated with a gluten-free diet for at least 1 year, and 30 control subjects were enrolled in this study. Dynamic contrast-enhanced MR imaging was performed by using a 1.5-T MR unit. For each MR imaging examination, maximum enhancement, slope of enhancement, and time-signal intensity curves were calculated at the level of the descending duodenal wall. Duodenal wall thickness was also evaluated. Statistical evaluation was performed by using one-way analysis of variance, and the results were confirmed by using the Bartlett test for equal variances and complemented by using Bonferroni multiple comparison, linear correlation, and the Student t test for paired data. RESULTS: Mean maximum enhancement of the duodenal wall was significantly higher in patients with untreated celiac disease (229.1 +/- 46.4 [standard deviation]) than in patients with treated celiac disease (109.8 +/- 27.8) and control subjects (94.7 +/- 17.9) (P < .001 for each comparison). All 60 untreated patients showed a curve characterized by fast enhancement and washout (type 4), while all 45 treated patients and the 30 control subjects showed a curve characterized by slow constant enhancement (type 2). Mean duodenal wall thickness was not significantly different between untreated patients (2.2 mm +/- 0.4), treated patients (2.0 mm +/- 0.3), and control subjects (2.0 mm +/- 0.4) (one-way analysis of variance, P = .4177; Bartlett test, P = .6951). CONCLUSION: The results of this study suggest that dynamic evaluation of the bowel wall by using contrast-enhanced MR imaging can be an effective and reproducible way to show the inflammation state in celiac disease.

[MRI of extraperitoneal rectal carcinoma]. / La diagnostica per immagini del carcinoma del retto sottoperitoneale.

Last years technological developments in imaging field have made a substantial contribution to diagnosis and staging of rectal cancer. Endorectal ultrasound and MRI with endorectal coil are very useful in rectal cancer initial staging thanks to their ability to distinguish between the rectal wall layers. Major ultrasound limitations are presence of inflammations, desmoplastic reaction and small field of view which limits evaluation of perirectal invasion. MRI with phased-array coils, instead, allows depiction of mesorectum and to assess the distance between tumor and mesorectal fascia. Unfortunately CT shows low accuracy compared to MRI in local staging because it fails to distinguish the rectal wall layers. The criterion used in assessing nodal involvement remains unfortunately still the dimensional one even if new contrast media based on nano-iron particles look promising in this regard On reassessment after chemo-radiotherapy treatment, MRI proved to be a very accurate tool thanks to its ability to detect tumor downstaging, disappearance of mesorectal fascia infiltration or even to show a complete response. The presence of recurrence can be studied by contrast enhanced perfusion-MRI or with good accuracy using PET which, however, presents major technical limitations at present.

Prospective study comparing multi-detector row CT and endoscopy in acute gastrointestinal bleeding.

BACKGROUND: Upper and lower acute gastrointestinal bleeding (AGIB) is associated with high rates of mortality and morbidity. The latest computerized tomography (CT) imaging techniques play an important role in the treatment of this pathology. METHODS: Twenty-nine patients with severe AGIB (11 upper, 18 lower), all hemodynamically stable, underwent endoscopy followed by a multi-detector row CT (MDCT) scan. Endoscopic and MDCT accuracy for the anatomical localization and etiology of AGIB was assessed, the diagnosis being considered correct when the two procedures were concordant or when the diagnosis was confirmed by angiographic, surgical, or post-mortem findings. RESULTS: The sensitivity in identifying the site and etiology of bleeding was, respectively, 100% and 90.9% for the MDCT scan, compared with 72.7% and 54.5% for endoscopy in upper AGIB, and 100% and 88.2% for the MDCT scan, compared with 52.9% and 52.9% for endoscopy, in lower AGIB. CONCLUSIONS: Considering the advantages of MDCT over endoscopy, we propose a new diagnostic algorithm for AGIB.

Small-bowel neoplasms: prospective evaluation of MR enteroclysis.

PURPOSE: To prospectively evaluate the accuracy of magnetic resonance (MR) enteroclysis in the detection of small-bowel neoplasms in symptomatic patients, with conventional endoscopy, tissue specimen, capsule endoscopy, conventional enteroclysis, and follow-up findings as reference standards. MATERIALS AND METHODS: The study protocol was approved by the human research committee, and all patients gave written informed consent. One hundred fifty patients (83 male, 67 female; mean age, 42.6 years; age range, 17-84 years) who were clinically suspected of having small-bowel neoplasm and whose previous upper and lower gastrointestinal endoscopy findings were normal underwent MR enteroclysis. The MR enteroclysis findings were prospectively evaluated for the presence of focal bowel wall thickening, small-bowel masses, and small-bowel stenosis. Positive MR enteroclysis findings were compared with histopathologic examination results obtained after surgical (n = 19) or endoscopic (n = 2) procedures. Negative MR enteroclysis results were compared with the results of enteroscopy (n = 5), capsule endoscopy (n = 53), or conventional enteroclysis with subsequent clinical follow-up (n = 71). The diagnostic performance of MR enteroclysis was analyzed on a per-patient basis. RESULTS: MR enteroclysis was successfully completed in all 150 patients and enabled correct detection of 19 small-bowel neoplasms, which were confirmed at histopathologic examination: three carcinoid neoplasms, two adenocarcinomas, two stromal tumors, five lymphomas, one angiomatous mass, three small-bowel metastases, one leiomyoma, one adenoma, and one lipoma. Overall sensitivity, specificity, and accuracy in identifying patients with small-bowel lesions were 86% (19 of 22), 98% (126 of 128), and 97% (145 of 150), respectively. Two MR enteroclysis examinations yielded false-positive findings, and three yielded false-negative findings. CONCLUSION: MR enteroclysis is an accurate modality for detecting small-bowel neoplasms in symptomatic patients.

Dynamic MR imaging of the pelvic floor: a pictorial review.

Pelvic floor dysfunctions involving some or all pelvic viscera are complex conditions that occur frequently and primarily affect adult women. Because abnormalities of the three pelvic compartments are frequently associated, a complete survey of the entire pelvis is necessary for optimal patient management, especially before surgical correction is attempted. With the increasing use of magnetic resonance (MR) imaging in assessing functional disorders of the pelvic floor, familiarity with normal imaging findings and features of pathologic conditions are important for radiologists. Dynamic MR imaging of the pelvic floor is an excellent tool for assessing functional disorders of the pelvic floor such as pelvic organ prolapse, outlet obstruction, and incontinence. Findings reported at dynamic MR imaging of the pelvic floor are valuable for selecting patients who are candidates for surgical treatment and for choosing the appropriate surgical approach. This pictorial essay reviews MR imaging findings of pelvic organ prolapse, fecal incontinence, and obstructed defecation. Supplemental material available at http://radiographics.rsnajnls.org/cgi/content/full/e35v1/DC1.

Endorectal and dynamic contrast-enhanced MRI for detection of local recurrence after radical prostatectomy.

OBJECTIVE: The objective of our study was to evaluate the sensitivity and specificity of endorectal MRI combined with dynamic contrast-enhanced MRI to detect local recurrence after radical prostatectomy. MATERIALS AND METHODS: A total of 51 patients who had undergone radical prostatectomy for prostatic adenocarcinoma 10 months to 6 years before underwent a combined endorectal coil MRI and dynamic gadolinium-enhanced MRI before endorectal sonographically guided biopsy of the prostatic fossa. The MRI combined with MR dynamic imaging results were correlated with the presence of recurrence defined as a positive biopsy result or reduction in prostate-specific antigen level after radiation therapy. RESULTS: Overall data of 46 (25 recurred, 21 nonrecurred) out of 51 evaluated patients were analyzed. All recurrences showed signal enhancement after gadolinium administration and, in particular, 22 of 24 patients (91%) showed rapid and early signal enhancement. The overall sensitivity and specificity of MR dynamic imaging was higher compared with MRI alone (88%, [95% CI] 69-98% and 100%, 84-100% compared with 48%, 28-69% and 52%, 30-74%). MRI combined with dynamic imaging allowed better identification of recurrences compared with MRI alone (McNemar test: chi-square(1) = 16.67; p = < 0.0001). CONCLUSION: MRI combined with dynamic contrast-enhanced MRI showed a higher sensitivity and specificity compared with MRI alone in detecting local recurrences after radical prostatectomy.

Comparison of MR enteroclysis with MR enterography and conventional enteroclysis in patients with Crohn's disease.

To prospectively compare the diagnostic accuracy of MR enteroclysis with duodenal intubation with MRI after drinking oral contrast agent only (MR enterography) with conventional enteroclysis (conv-E) as reference standard in patients with Crohn's disease. Forty consecutive patients (22 males and 18 females; mean age 36; range 16-74 years) with proven Crohn's disease underwent conv-E and MR imaging. Twenty-two patients underwent MR enteroclysis with intubation (MRE) and 18 underwent MR-enterography (MR per OS). Two radiologists reached a consensus about the following imaging findings: luminal distension and visualization of superficial mucosal, mural and mesenteric abnormalities. Standard descriptive statistics and a Wilcoxon rank sum test were used. Statistical significance was inferred at P < 0.05. There was no significant difference in the adequacy of luminal distention between the MRE and conv-E (P = 0.08), and both were statistically superior in comparison to MR per OS in the distension of the jejunum (P < 0.01) and less significant at the ileum and terminal ileum levels (P < 0.05). MRE and conv-E were comparable for the accuracy of superficial mucosal abnormalities; meanwhile conv-E compared with MR per OS was statistically superior (P < 0.01). MRE compared with MR per OS was statistically better when visualizing superficial abnormalities (P < 0.01). No statistically significant differences were found in assessing the diagnostic efficacy between MR examinations for the depiction of mural stenosis (P = 0.105) and fistulae (P = 0.67). The number of detected mesenteric findings was significantly higher with both MRE and MR per OS compared to conv-E (P < 0.01). MRE can serve as the diagnostic procedure for initially evaluating patients suspected of having Crohn's disease. MR per OS may have a role in patients that refuse or have failed intubation and also for follow-up.

Contribution of the MR spectroscopic imaging in the diagnosis of prostate cancer in the peripheral zone.

PURPOSE: To establish the additional value of 3D magnetic resonance spectroscopy (3D-MRS) imaging to endorectal MR imaging in the diagnosis of prostrate cancer in the peripheral zone. MATERIALS AND METHODS: MR imaging and MRS imaging were performed in 79 patients with suspicion of prostate cancer on the basis of digital rectal exploration, transrectal ultrasound and PSA level. All the examinations were performed with 1.5 T MR scan using an endorectal coil (transverse and coronal FSE T2-weighted sequences, axial SE T1-weighted and PRESS 3D CSI). MR examinations have been evaluated by two Radiologists blind of the clinical data in a "per patients" analysis. MR imaging and MRS imaging findings were compared with the result of histological data from radical prostatectomy in 53 patients and biopsy in 17 patients. RESULTS: Nine patients (11.4%) were excluded because of serious artefacts in the MR spectrum. The reported values of sensitivity, specificity, PPV and NPV for MR imaging alone were respectively 84%, 50%, 76% and 63% (LR+ 1.7; LR- 0.3). Instead the reported values of sensitivity, specificity, PPV and NPV for the combination of MR imaging to MRS imaging were respectively 89%, 79%, 89% and 79% (LR+ 4.28; LR- 0.14). We found an incremental benefit of MRS imaging to MR imaging for tumour diagnosis although these results did not show statistically significant differences. CONCLUSIONS: The MRS imaging improves the accuracy of the endorectal MR imaging in the diagnosis of prostate cancer.