Ferumoxytol-Enhanced MRI in Imaging Lymph Nodes in Patients With Locally Advanced Rectal Cancer

Inclusion Criteria:

* Pathologically confirmed, locally advanced, malignancy of the rectum; based on multi-disciplinary tumor board discussion, patients are candidates for tri-modality treatment
* Stage T1-4bN1-2, by the American Joint Committee on Cancer (AJCC) 7th edition, based on the following minimum workup:

  * CT chest/abdomen with contrast
  * MRI pelvis with contrast
  * PET/CT of the whole-body or skull base to mid-thigh
* Subjects must have had no prior therapy for cancer of the rectum
* Members of all races and ethnic groups will be included
* Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
* White blood cell count \>= 3.0 K/cu mm
* Absolute neutrophil count \>= 1.5 K/cu mm
* Platelets \>= 100 K/cu mm
* Hemoglobin \>= 8.0 g/dl (the use of transfusion or other invention to achieve hemoglobin \[Hgb\] \>= 8.0 g/dl is acceptable)
* Total bilirubin =\< 1.5 X institutional upper limit of normal
* Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 X institutional upper limit of normal
* Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for subjects with creatinine levels above institutional normal
* Woman of childbearing potential, a negative serum or urine pregnancy test
* Willingness to use adequate contraception for 12 months after completion of all therapy
* Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

* Subjects with AJCC 7th edition stage TxN0 and/or metastatic disease outside of pelvis (suspicious lateral pelvic lymph nodes up to and including common iliacs are allowed on the protocol)
* Prior systemic chemotherapy for rectal cancer; prior chemotherapy for another malignancy is allowable as long as it has been \> 2 years since completion of therapy for previous malignancy
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ferumoxytol or other agents used in the study
* Prior abdominopelvic radiation or radiation for rectal cancer
* History of other malignancy in the past 2 years except non-melanomatous skin cancer, breast ductal carcinoma in situ (DCIS) and low-risk prostate adenocarcinoma
* Medical contraindications to low anterior resection or abdominoperineal resection
* Uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant women are excluded from this study because chemoradiotherapy has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to the use of ferumoxytol as a contrast agent in the mother, breastfeeding should be discontinued if the mother receives ferumoxytol while nursing; men who are sexually active and not willing/able to use medically acceptable forms of contraception are also excluded from this study
* Subjects with multiple drug allergies and/or subjects who have had an allergic reaction to any intravenous iron replacement product or a known history of hypersensitivity to ferumoxytol
* Subjects with concurrent clinical diagnosis of evidence of active iron overload defined by the following 1) ferritin \>= 250 ng/mL in men or \>= 200 ng/mL in women AND 2) transferrin saturation, the ratio of plasma iron to transferrin, expressed as percent, \>= 45%
* Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with ferumoxytol
* Patients with renal insufficiency; glomerular filtration rate (GFR) \< 60
* Adult patients who require monitored anesthesia for MRI scanning
* Subjects who have a contraindication for MRI: metal in their bodies (a cardiac pacemaker or other incompatible device), are severely agitated, or have an allergy to gadolinium (Gd) contrast material
* Subjects with known hepatic insufficiency or cirrhosis as determined by either a prior diagnosing physician or at review at initial consultation; these disease entities do not have formal associated lab values and are thus a clinical diagnosis by the prior aforementioned physician