Stem cell therapies aim to replace abnormal, injured, or lost cells in organs with little or no capacity for self-renewal and provide hope for cures of devastating diseases with previously presumed irreversible functional loss, such as myocardial or brain infarction, blindness, paraplegia, diabetes mellitus, and degenerative or post-traumatic bone/ cartilage defects, among many others. In order to treat a cellular and/or functional deficit in a selected target organ, stem cells or stem-cell-derived cell populations are administered systemically (e.g. into the blood system), into a cavity (e.g. into a brain ventricle), or directly into target tissue (e.g. into myocardium). Many questions arise about the fate of the administered cells. Do the stem cells actually end up where they are desired (homing)? Do they survive? Do they integrate themselves with the host tissue (engraftment)? If undifferentiated stem cells are transplanted, do these cells differentiate into the desired specialized progenies and restore the impaired function of the target tissue? Does the host's immune system tolerate or reject the transplanted cells? Noninvasive imaging techniques can address these questions and help to develop and monitor successful approaches for stem-cell-mediated tissue regeneration.

Methods to Visualize Stem Cell Homing and Engraftment

There are various classical methods of showing distribution of stem cells in the body. Most rely on introducing a marker into the graft material that can be specifically stained after explantation. One common method is the transfection of stem cells with a plasmid containing lacZ. lacZ encodes β-galactosidase, an enzyme not normally found in human cells. After explantation, fixation, and staining of material to be examined, marked cells will stain while unmarked cells will not. This method is applicable only in animal models. Another common pre-clinical method is the transfection of stem cells with luciferase genes. Luciferase catalyzes a two-step chemical reaction of the substrate luciferin, which leads to bioluminescence detectable in vivo by an optical imaging system. Photon generation following intravenous administration of luciferin takes place exclusively at the site of luciferase expression; therefore, the target-to-background signal ratio is extremely high. Bioluminescence imaging has been used for cell tracking in small animal models. However, limitations for human application for cell tracking are poor spatial resolution, the need to inject high doses of luciferin to generate a contrast effect, and potential immunogenicity of the foreign gene protein, luciferase.

Imaging description

A 14-year-old girl presented with seizures. The clinical examination revealed wart-like, small 4–5 mm, brownish nodules of the face with a bimalar distribution as well as palpable flank masses bilaterally. An ultrasound of the kidneys demonstrated multiple renal cysts bilaterally (Fig. 57.1a). Color Doppler evaluation did not reveal any vascular abnormality (Fig. 57.1a). A CT confirmed the cystic nature of the renal lesions (Fig. 57.1b); there was no evidence for solid renal masses. Tuberous sclerosis was suggested as the most likely diagnosis.

Criteria for uncomplicated renal cysts on ultrasound scans include the presence of an anechoic, round or oval structure with sharply circumscribed smooth walls and enhanced through-transmission. On CT scans, criteria for a cyst include a round or oval well-defined lesion with water attenuation, sharply circumscribed smooth walls, and lack of enhancement or fat attenuation. On MR images, a cyst is defined as a lesion that demonstrates fluid signal intensity on T1- (dark) and T2- (bright) weighted images, with round, well-defined borders and sharply circumscribed smooth walls, and no contrast enhancement.

Imaging description

A term infant presented with generalized anasarca, pleural effusion, and acites. A radiograph of the chest and abdomen/pelvis confirmed marked, generalized soft tissue swelling and bilateral pleural effusions (Fig. 81.1). There were several focal, round calcifications projecting below the right 12th rib, at the expected location of the gallbladder. An ultrasound confirmed numerous gallstones in the gallbladder (Fig. 81.2). There was no evidence of gallbladder wall thickening, pericholecystic fluid, cholestasis, or other abnormalities of the bile ducts.

Importance

A hydrops fetalis is defined by the presence of fluid accumulation in at least two anatomic compartments in the fetus or newborn. Based on its etiology, two types of hydrops fetalis are distinguished: immune hydrops and non-immune hydrops. Gallstones are frequently noted in patients with immune-mediated hydrops, but not in patients with non-immune causes of hydrops. Hydrops fetalis is a serious condition, which can result in death of the infant shortly before or after delivery.

Imaging description

An infant presented with hematuria and thrombocytopenia. An ultrasound and subsequent CT scan demonstrated a thrombus in the right renal vein with an enlarged edematous right kidney (Fig. 59.1). The CT demonstrated diminished contrast enhancement of the medial/posterior aspect of the kidney (Fig. 59.1b) and a thrombus in the inferior vena cara (IVC), which extended into the right renal vein.

Importance

Renal vein thrombosis is the most common vascular pathology of the newborn kidney. Predisposing factors in a neonate include dehydration, sepsis, birth asphyxia, maternal diabetes, polycythemia, adrenal hemorrhage, and the presence of an indwelling catheter. In older children, renal vein thrombosis is associated with nephrotic syndrome and membranous glomerulonephritis, renal tumor (most commonly Wilms’ tumor; see Case 64), phlebitis, renal amyloidosis, hereditary thrombophilia, and other hypercoaguable states as well as trauma and burns. The prognosis for the affected kidney is very poor. Anticoagulant and fibrinolytic therapies rarely lead to successful reperfusion. In a few patients, the kidney may recover completely. However, much more frequently, late sequelae are observed, such as focal or complete atrophy of the kidney, impaired renal function, and arterial hypertension.

Imaging description

A seven-year-old boy presented with nausea and acute, colicky abdominal pain. The medical history revealed a pharyngitis a few weeks ago and the clinical examination demonstrated multiple small purpura (small areas of hemorrhage) of the skin of the buttocks and upper thighs. An upper gastrointestinal (GI) study demonstrated “thumbprinting” of the duodenum (Fig. 46.1). CT images from another patient after oral contrast media administration demonstrate marked mural thickening of a loop of ileum with narrowing of the lumen and some adjacent free fluid (Fig. 46.2).

Importance

Henoch–Schönlein purpura is a disease of young children (50% are younger than six years of age and 90% are younger than 10 years of age), which typically occurs after an upper respiratory tract infection. The infection leads to formation of complexes of IgA and complement component 3, which accumulate in small vessels and cause a small-vessel vasculitis of the skin, joints, GI tract, and sometimes the kidneys. Acute GI symptoms may precede typical cutaneous lesions in 10–15% of patients and may lead to a laparotomy. It is important to recognize typical clinical and imaging findings of this disease, since it usually resolves spontaneously and does not require invasive interventions.

Imaging description

A 22-month-old female presented with a history of vomiting and a palpable right abdominal mass. An abdominal ultrasound (not shown) and an MRI of the abdomen (Fig. 64.1) demonstrated a large mass involving the right kidney, with distortion of the pelvicalyceal system. In addition a large tumor thrombus was noted in the right renal vein, extending into the inferior vena cava (IVC) to the level of the mid liver with marked dilatation of these vessels. The tumor thrombus also extended into the left renal vein, up to the renal hilum (Fig. 64.1). A renal biopsy confirmed the diagnosis of a Wilms’ tumor (WT).

Importance

WT is the most common renal neoplasm in children, with 95% of cases occurring between 2 and 5 years of age. Five to seven percent of children have bilateral disease with 7% of cases being multicentric (Fig. 64.2). Nephrogenic rests, which are thought to be precursors of WT, are seen in 1% of neonates and it is believed that only 1% of these transform into WT. Histologically, WTs are of triphasic cell lineage comprising blastemal, stromal, and epithelial cells and about 7% are anaplastic. Favorable histology WT have absence of anaplasia, have a better prognosis, and are more responsive to chemotherapy. Unfavorable histology WTs exhibit anaplasia, are chemotherapy resistant, and are associated with an increased risk of recurrence.

Imaging description

A two-year-old boy presented with leukocoria (= white pupil). Ophthalmoscopy demonstrated large masses in both globes. A CT scan showed extensive calcifications of both lesions (Fig. 1.1a). An MR scan better delineated the contrast-enhancing masses in the bilateral globes, both of which demonstrated extraocular extension (Fig. 1.1b).

An axial contrast-enhanced MR scan of the brain in a different patient with retinoblastoma shows an additional, inhomogeneously enhancing mass in the pineal gland (Fig. 1.2).

Importance

Retinoblastoma is the most common intraocular tumor of childhood, occurring in one in 15000 to 20000 live births. Approximately 200 new cases a year are diagnosed in the USA. The disease presents in infancy or early childhood, with the majority of cases diagnosed before the age of 4 years.

A second primary malignancy, most commonly a midline intracranial tumor, is found in 5–7% of patients with bilateral retinoblastoma. Often, these other brain tumors occur weeks or months after the diagnosis of the retinoblastoma, with a median interval of 21 months. Trilateral retinoblastoma has traditionally been nearly universally fatal, although a recent study suggests that intensive chemotherapy may improve survival. Early detection is likely an important factor in survival.

Imaging description

A longitudinal ultrasound of the right scrotum (Fig. 73.1) in a 13-year-old boy with gradual onset of testicular pain demonstrates a well-defined oval hypoechoic avascular structure located in the groove between the testis and epididymis. There was mild hyperemia of the testis and epididymis, which were otherwise normal in appearance. A moderate hydrocele and scrotal wall edema was also noted. These findings were suggestive of torsion of the appendix testis.

Importance

Testicular appendages are remnants of embryonic mesonephric and paramesonephric ducts and consist of vascularized connective tissue. Five types of appendages have been identified. The appendix testis is a tiny structure, 1–7 mm in size, located at the upper pole of the testis, in the groove between the testis and epididymis. It has similar echogenicity to the testis and may be oval or sessile and less commonly pedunculated. It is present in 92% of patients and is the commonest appendage to undergo torsion. The appendix epididymis is located at the head of the epididymis, is commonly pedunculated, and is less frequently seen on ultrasound. The other appendages are difficult to identify on ultrasound imaging.

Imaging description

A 16-year-old female patient presented with a two-week history of increasing fever, back pain, and dysuria. The clinical evaluation revealed tenderness in the left flank, an elevated C-reactive protein, and leukocytosis. An ultrasound (US) of the kidneys demonstrated a focal lesion of uncertain etiology in the left kidney. A CT scan was obtained for further evaluation and showed two focal wedge-shaped hypodense lesions in the left kidney (Fig. 60.1) suggestive of acute focal pyelonephritis. The patient was placed on antibiotic treatment, which led to resolution of the lesions.

In the clinical setting of fever and laboratory signs of an infection, focal lesions in the kidneys as described above should be considered to be acute bacterial pyelonephritis, previously called “lobar nephronia.”

Renal US examination in a child with acute pyelonephritis is often completely normal and is less sensitive than other imaging modalities such as CT, MR, or nuclear scintigraphy. There may be focal hypo- or hyperechoic areas, depending on the degree of associated edema and/or hemorrhage. In some cases, the focal area of inflammation may produce mass effect on adjacent structures. Color Doppler US, especially power Doppler, tends to show decreased flow in these areas. Diffuse renal involvement may produce diffuse enlargement with hypo- or hyperechogenicity, loss of corticomedullary differentiation, and uro-epithelial thickening. There may be additional features of an underlying renal obstructive anomaly predisposing to infection, including an obstructed duplicated upper pole collecting system, ureteropelvic or ureterovesical obstruction.

Imaging description

A seven-year-old boy presented with nausea, right upper abdominal pain, and jaundice. An initial ultrasound (not shown) demonstrated a cystic lesion in the area of the porta hepatis, separate from the gallbladder. Axial and coronal T2-weighted MR images and 3D MRCP demonstrated fusiform dilatation of the central hepatic ducts and the common bile duct, consistent with a type I choledochal cyst (CC) (Fig. 45.1a–k). The intrahepatic bile ducts appeared normal in caliber. There was no evidence for choledocholithiasis or pancreatitis. An endoscopic retrograde cholangiopancreatography (ERCP) confirmed contrast filling of a fusiform dilated common bile duct without associated dilatation of the intrahepatic bile ducts (Fig. 45.1).

Importance

CCs represent congenital dilatation(s) of the extrahepatic and/or intrahepatic biliary system. The initial diagnostic workup usually entails an abdominal ultrasound, which demonstrates an anechoic cystic structure in the region of the porta hepatis, separate from the gallbladder. Depending on the extent of the cyst, five different types are recognized according to the classification system of Todani (Fig. 45.2). Type I is the most common type, comprising 80–90% of CCs, and representing a fusiform or cystic dilatation of the extrahepatic biliary system. A mild, secondary dilatation of the more proximal intrahepatic biliary system may be visualized; however, the more peripheral intrahepatic bile ducts are typically not dilated.

Imaging description

A neonate who was a few days old presented with acute bilious vomiting. A radiograph of the abdomen demonstrated a “double bubble” sign with air in the stomach and the duodenum, but no air in more distal loops of bowel. An upper gastrointestinal (GI) fluoroscopy after oral administration of thin barium solution revealed an obstruction of the proximal duodenum and a “corkscrew” appearance of subsequent small bowel loops (Fig. 50.1). These findings are characteristic for malrotation of the small bowel and midgut volvulus around the mesenteric axis (Fig. 50.2).

Importance

Bowel malrotation occurs when there is abnormal rotation of the bowel in utero, resulting in absence of the normal broad mesenteric fixation from the left upper quadrant (proximal jejunum–ligament of Treitz) to the right lower quadrant (cecal fixation). As a result the mesentery and accompanying vessels have a narrow stalk-like configuration. Midgut volvulus is characterized by rotation of the proximal small bowel around the mesenteric stalk with variable compromise of the blood supply to the bowel. Affected bowel may extend from the proximal duodenum to the mid transverse colon. Arterial compromise may lead to mucosal necrosis, pneumatosis, perforation, peritonitis, and death. Thus, immediate and emergent evaluation is warranted in a case of suspected midgut volvulus.

Imaging description

A four-year-old boy presented with large palpable flank masses bilaterally. An ultrasound (not shown) revealed bilaterally enlarged kidneys with homogeneous low echogenicity, resembling renal cortex. A contrast-enhanced CT was performed which showed a thick rim of non-enhancing, homogeneous soft tissue, surrounding centrally enhancing renal parenchyma (Fig. 62.1). Bilateral homogeneous non-enhancing soft tissue surrounding the renal parenchyma is a typical finding in diffuse bilateral nephroblastomatosis. Another patient with a similar presentation is shown in Figure 62.2. In this case, axial contrast-enhanced CT images demonstrate multiple lenticular, uniform, non-enhancing lesions in the renal cortex (Fig. 62.2), consistent with the more common multifocal type of nephroblastomatosis. On CT, focal nephroblastomatosis appears as low attenuation, subcapsular, or intraparenchymal lesions with poor enhancement relative to that of adjacent normal renal parenchyma. On MRI, focal nephroblastomatosis demonstrates low to intermediate signal intensity foci on both T1- and T2-weighted sequences. Both types of nephroblastomatosis typically resemble the normal renal cortex with regard to their echogenicity on ultrasound, and density and signal intensity on unenhanced CT and MRI. After contrast media injection, however, the lesions typically show no or only minimal enhancement. Contrast administration is helpful in differentiating nephroblastomatosis from Wilms’ tumor. The latter is typically inhomogeneous and enhances after contrast media administration.

Imaging description

An 11-year-old patient presented with diffuse abdominal pain. The medical history, clinical examination, and laboratory values did not reveal any abnormal findings. A fluoroscopic barium upper gastrointestinal (GI) study with small bowel follow through (SBFT) revealed multiple 2 mm nodules on the mucosal surface of the terminal ileum, deforming the thin barium-filled parallel folds that are seen in the contracted ileum (Fig. 49.1). These mucosal nodules are typical of benign enlarged lymphoid follicles, a frequent finding in children and adolescents. Additional examples are shown in (Figs. 49.2 and 49.3).

Importance

Lymphoid follicular hyperplasia of the intestinal tract represents a benign enlargement of the submucosal lymphoid follicles. It is a common condition in children and adolescents. The lesions may present in two forms, a focal or a diffuse type. In the more common focal type, an aggregate of benign lymphoid nodules is found in an isolated area, usually the terminal ileum. In the less common diffuse form, a multinodular pattern is found throughout much of the GI tract, especially the colon. The diffuse follicular hyperplasia may be seen in children with GI infections and/or bleeding and perhaps represents a lymphoid reaction to an unidentified infection. Especially when found in the colon, benign follicular hyperplasia has been confused with multiple polyposis, leading to unnecessary surgery or endoscopic resections. Follicular lymphoid hyperplasia of the appendix is associated with dilatation and thickening of the mucosa and can be mistaken for appendicitis or other pathology (Fig. 49.3). Absence of wall thickening, hyperemia, and periappendiceal inflammation help in making this distinction.